Molecular and serum markers in hepatocellular carcinoma: Predictive tools for prognosis and recurrence

Critical Reviews in Oncology/Hematology

Volumn 82, Issue 2, 2012, Pages 116-140

  Singhal, Ashish ^a   Jayaraman, Muralidharan ^b   Dhanasekaran, Danny N ^b   Kohli, Vivek ^a  

^a INTEGRIS Nazih Zuhdi Transplant Institute   (United States)

^b UNIVERSITY OF OKLAHOMA HEALTH SCIENCES CENTER   (United States)

Author keywords

Biomarkers; Cancer; Carcinoma; Genetic; HCC; Hepatocellular; Liver; Markers; MiRNA; Molecular; Prognosis; Recurrence; Serum; Survival; Tissue

Indexed keywords

BETA CATENIN; CELLULAR APOPTOSIS SUSCEPTIBILITY PROTEIN; CYCLIN A; CYCLIN D1; CYCLIN DEPENDENT KINASE INHIBITOR; CYCLIN E; CYCLINE; DNA TOPOISOMERASE (ATP HYDROLYSING); END BINDING PROTEIN 1; GUANOSINE TRIPHOSPHATASE; HERMES ANTIGEN; INTERCELLULAR ADHESION MOLECULE 1; KI 67 ANTIGEN; MATRIX METALLOPROTEINASE; OSTEOPONTIN; PLAKOGLOBIN; PROTEIN BCL 2; PROTEIN BCL XL; PROTEIN MDM2; RHOC GTPASE; SORAFENIB; SURVIVIN; TELOMERASE; TOPOISOMERASE II ALPHA; TRANSCRIPTION FACTOR ETS 1; TUMOR MARKER; UNCLASSIFIED DRUG; UNINDEXED DRUG; UROKINASE; UVOMORULIN; WNT1 PROTEIN;

ANEUPLOIDY; ANGIOGENESIS; APOPTOSIS; CANCER CELL; CANCER DIAGNOSIS; CANCER INVASION; CANCER RECURRENCE; CELL ADHESION; CELL DIVISION; CELL NUCLEUS; CELL PROLIFERATION; CHROMOSOMAL INSTABILITY; CHROMOSOME 11Q; CHROMOSOME 13Q; CHROMOSOME 8P; CHROMOSOME 8Q; DISEASE FREE SURVIVAL; DNA METHYLATION; EXTRACELLULAR MATRIX; GENE; GENE EXPRESSION; GENE MUTATION; GENE OVEREXPRESSION; GENETIC SCREENING; HETEROZYGOSITY LOSS; HUMAN; LIVER CARCINOGENESIS; LIVER CELL CARCINOMA; LIVER RESECTION; LIVER TRANSPLANTATION; MDM2 GENE; METASTASIS; MICROSATELLITE INSTABILITY; MICROVASCULATURE; MICROVESSEL DENSITY; MORPHOLOGY; NUCLEAR MORPHOMETRY; ONCOGENE NEU; OVERALL SURVIVAL; P53 GENE; PROGNOSIS; PROTEIN EXPRESSION; RESTRICTION LANDMARK GENOMIC SCANNING; REVIEW; RHOC GENE; SURVIVAL RATE; TOP2A GENE; TUMOR BIOPSY; TUMOR DIFFERENTIATION; TUMOR SUPPRESSOR GENE;

ANTIGENS, NEOPLASM; CARCINOMA, HEPATOCELLULAR; CELL ADHESION; EXTRACELLULAR MATRIX; HUMANS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; LIVER NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; PROGNOSIS; RECURRENCE; TUMOR MARKERS, BIOLOGICAL;

EID: 84859433790     PISSN: 10408428     EISSN: 18790461     Source Type: Journal    
DOI: 10.1016/j.critrevonc.2011.05.005     Document Type: Review

References (224)

1. Marrero J.A. Hepatocellular carcinoma. Curr Opin Gastroenterol 2006, 22(3):248-253.
2. Motola-Kuba D., Zamora-Valdes D., Uribe M., Mendez-Sanchez N. Hepatocellular carcinoma. An overview. Ann Hepatol 2006, 5(1):16-24.
3. Blum H.E. Hepatocellular carcinoma: therapy and prevention. World J Gastroenterol 2005, 11(47):7391-7400.
4. Jemal A., Murray T., Ward E., et al. Cancer statistics, 2005. CA Cancer J Clin 2005, 55(1):10-30.
5. El-Serag H.B. Epidemiology of hepatocellular carcinoma. Clin Liver Dis 2001, 5:87-107.
6. Bismuth H., Majno P.E., Adam R. Liver transplantation for hepatocellular carcinoma. Semin Liver Dis 1999, 19(3):311-322.
7. Zavaglia C., De Carlis L., Alberti A.B., et al. Predictors of long-term survival after liver transplantation for hepatocellular carcinoma. Am J Gastroenterol 2005, 100(12):2708-2716.
8. Zimmerman M.A., Ghobrial R.M., Tong M.J., et al. Recurrence of hepatocellular carcinoma following liver transplantation. A Review of preoperative and postoperative prognostic indicators. Arch Surg 2008, 143(2):182-188.
9. Lai E.C., Ng I.O., Ng M.M., et al. Long-term results of resection for large hepatocellular carcinoma: a multivariate analysis of clinicopathological features. Hepatology 1990, 11(5):815-818.
10. Shirabe K., Kanematsu T., Matsumata T., Adachi E., Akazawa K., Sugimachi K. Factors linked to early recurrence of small hepatocellular carcinoma after hepatectomy: univariate and multivariate analyses. Hepatology 1991, 14(5):802-805.
11. Jwo S.C., Chiu J.H., Chau G.Y., Loong C.C., Lui W.Y. Risk factors linked to tumor recurrence of human hepatocellular carcinoma after hepatic resection. Hepatology 1992, 16(6):1367-1371.
12. Ikeda K., Saitoh S., Tsubota A., et al. Risk factors for tumor recurrence and prognosis after curative resection of hepatocellular carcinoma. Cancer 1993, 71(1):19-25.
13. Giannelli G., Antonaci S. Novel concepts in hepatocellular carcinoma: from molecular research to clinical practice. J Clin Gastroenterol 2006, 40(9):842-846.
14. Cha C., Dematteo R.P. Molecular mechanisms in hepatocellular carcinoma development. Best Pract Res Clin Gastroenterol 2005, 19(1):25-37.
15. Farazi P.A., DePinho R.A. Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer 2006, 6(9):674-687.
16. Mann C.D., Neal C.P., Garcea G., Manson M.M., Dennison A.R., Berry D.P. Prognostic molecular markers in hepatocellular carcinoma: a systematic review. Eur J Cancer 2007, 43(6):979-992.
17. Qin L.X., Tang Z.Y. The prognostic molecular markers in hepatocellular carcinoma. World J Gastroenterol 2002, 8(3):385-392.
18. Travali S., Ku D.H., Rizzo M.G., Ottavio L., Baserga R., Calabretta B. Structure of the human gene for the proliferating cell nuclear antigen. J Biol Chem 1989, 264(13):7466-7472.
19. Korkolopoulou P., Patsouris E., Pangalis G., et al. A comparative assessment of proliferating cell nuclear antigen, c-myc p62, and nucleolar organizer region staining in non-Hodgkin's lymphomas: a histochemical and immunohistochemical study of 200 cases. Hum Pathol 1993, 24(4):371-377.
20. Ng I.O., Lai E.C., Fan S.T., Ng M., Chan A.S., So M.K. Prognostic significance of proliferating cell nuclear antigen expression in hepatocellular carcinoma. Cancer 1994, 73(9):2268-2274.
21. Hino N., Higashi T., Nouso K., et al. Proliferating cell nuclear antigen and grade of malignancy in small hepatocellular carcinoma - evaluation in US-guided specimens. Hepatogastroenterology 1997, 44(13):245-250.
22. Lin G.Y., Chen Z.L., Lu C.M., Li Y., Ping X.J., Huang R. Immunohistochemical study on p53, H-rasp21, c-erbB-2 protein and PCNA expression in HCC tissues of Han and minority ethnic patients. World J Gastroenterol 2000, 6(2):234-238.
23. Stroescu C., Dragnea A., Ivanov B., et al. Expression of p53, Bcl-2, VEGF, Ki67 and PCNA and prognostic significance in hepatocellular carcinoma. J Gastrointest Liver Dis 2008, 17(4):411-417.
24. Osada S., Saji S., Kuno T. Clinical significance of combination study of apoptotic factors and proliferating cell nuclear antigen in estimating the prognosis of hepatocellular carcinoma. J Surg Oncol 2004, 85(1):48-54.
25. Nan K.J., Guo H., Ruan Z.P., Jing Z., Liu S.X. Expression of p57 (kip2) and its relationship with clinicopathology, PCNA and p53 in primary hepatocellular carcinoma. World J Gastroenterol 2005, 11(8):1237-1240.
26. Bullwinkel J., Baron-Luhr B., Ludemann A., Wohlenberg C., Gerdes J., Scholzen T. Ki-67 protein is associated with ribosomal RNA transcription in quiescent and proliferating cells. J Cell Physiol 2006, 206(3):624-635.
27. Scholzen T., Gerdes J. The Ki-67 protein: from the known and the unknown. J Cell Physiol 2000, 182(3):311-322.
28. Cui J., Dong B.-W., Liang P., Yu X.-L., Yu D.-J. Effect of c-myc, Ki-67, MMP-2 and VEGF expression on prognosis of hepatocellular carcinoma patients undergoing tumor resection. World J Gastroenterol 2004, 10(10):1533-1536.
29. Guzman G., Alagiozian-Angelova V., Layden-Almer J.E., et al. p53, Ki-67, and serum alpha feto-protein as predictors of hepatocellular carcinoma recurrence in liver transplant patients. Mod Pathol 2005, 18(11):1498-1503.
30. Fiorentino M., Altimari A., Ravaioli M., et al. Predictive value of biological markers for hepatocellular carcinoma patients treated with orthotopic liver transplantation. Clin Cancer Res 2004, 10(5):1789-1795.
31. Behrens P., Brinkmann U., Wellmann A. CSE1L/CAS: its role in proliferation and apoptosis. Apoptosis 2003, 8(1):39-44.
32. Brinkmann U. CAS, the human homologue of the yeast chromosome-segregation gene CSE1, in proliferation, apoptosis, and cancer. Am J Hum Genet 1998, 62(3):509-513.
33. Wellmann A., Flemming P., Behrens P., et al. High expression of the proliferation and apoptosis associated CSE1L/CAS gene in hepatitis and liver neoplasms: correlation with tumor progression. Int J Mol Med 2001, 7(5):489-494.
34. Shiraki K., Fujikawa K., Sugimoto K., et al. Cellular apoptosis susceptibility protein and proliferation in human hepatocellular carcinoma. Int J Mol Med 2006, 18(1):77-81.
35. Liao C.F., Luo S.F., Li L.T., Lin C.Y., Chen Y.C., Jiang M.C. CSE1L/CAS, the cellular apoptosis susceptibility protein, enhances invasion and metastasis but not proliferation of cancer cells. J Exp Clin Cancer Res 2008, 27:15.
36. Ikeguchi M., Sato N., Hirooka Y., Kaibara N. Computerized nuclear morphometry of hepatocellular carcinoma and its relation to proliferative activity. J Surg Oncol 1998, 68(4):225-230.
37. Veltri R.W., Partin A.W., Miller M.C. Quantitative nuclear grade (QNG): a new image analysis-based biomarker of clinically relevant nuclear structure alterations. J Cell Biochem Suppl 2000, Suppl. 35:151-157.
38. Blaszyk H., Hartmann A., Cunningham J.M., et al. A prospective trial of midwest breast cancer patients: a p53 gene mutation is the most important predictor of adverse outcome. Int J Cancer 2000, 89(1):32-38.
39. Kahlenberg M.S., Stoler D.L., Rodriguez-Bigas M.A., et al. p53 tumor suppressor gene mutations predict decreased survival of patients with sporadic colorectal carcinoma. Cancer 2000, 88(8):1814-1819.
40. Ireland A.P., Shibata D.K., Chandrasoma P., Lord R.V., Peters J.H., DeMeester T.R. Clinical significance of p53 mutations in adenocarcinoma of the esophagus and cardia. Ann Surg 2000, 231(2):179-187.
41. Tamas L., Kraxner H., Mechtler L., et al. Prognostic significance of P53 histochemistry and DNA histogram parameters in head and neck malignancies. Anticancer Res 2000, 20(5C):4031-4037.
42. Mitsudomi T., Hamajima N., Ogawa M., Takahashi T. Prognostic significance of p53 alterations in patients with non-small cell lung cancer: a meta-analysis. Clin Cancer Res 2000, 6(10):4055-4063.
43. Shahin M.S., Hughes J.H., Sood A.K., Buller R.E. The prognostic significance of p53 tumor suppressor gene alterations in ovarian carcinoma. Cancer 2000, 89(9):2006-2017.
44. Soini Y., Virkajarvi N., Lehto V.P., Paakko P. Hepatocellular carcinomas with a high proliferation index and a low degree of apoptosis and necrosis are associated with a shortened survival. Br J Cancer 1996, 73(9):1025-1030.
45. Sheen I.S., Jeng K.S., Wu J.Y. Is p53 gene mutation an indicatior of the biological behaviors of recurrence of hepatocellular carcinoma?. World J Gastroenterol 2003, 9(6):1202-1207.
46. Itoh T., Hayashi Y., Kanamaru T., et al. Clinical significance of urokinase-type plasminogen activator activity in hepatocellular carcinoma. J Gastroenterol Hepatol 2000, 15(4):422-430.
47. Jeng K.S., Sheen I.S., Chen B.F., Wu J.Y. Is the p53 gene mutation of prognostic value in hepatocellular carcinoma after resection?. Arch Surg 2000, 135(11):1329-1333.
48. Shiota G., Kishimoto Y., Suyama A., et al. Prognostic significance of serum anti-p53 antibody in patients with hepatocellular carcinoma. J Hepatol 1997, 27(4):661-668.
49. Qin L.X., Tang Z.Y., Ma Z.C., et al. P53 immunohistochemical scoring: an independent prognostic marker for patients after hepatocellular carcinoma resection. World J Gastroenterol 2002, 8(3):459-463.
50. Sugo H., Takamori S., Kojima K., Beppu T., Futagawa S. The significance of p53 mutations as an indicator of the biological behavior of recurrent hepatocellular carcinomas. Surg Today 1999, 29(9):849-855.
51. Lowe S.W., Bodis S., McClatchey A., et al. p53 status and the efficacy of cancer therapy in vivo. Science 1994, 266(5186):807-810.
52. Endo K., Ueda T., Ohta T., Terada T. Protein expression of MDM2 and its clinicopathological relationships in human hepatocellular carcinoma. Liver 2000, 20(3):209-215.
53. Tannapfel A., Wasner M., Krause K., et al. Expression of p73 and its relation to histopathology and prognosis in hepatocellular carcinoma. J Natl Cancer Inst 1999, 91(13):1154-1158.
54. Katoh H., Shibata T., Kokubu A., et al. Genetic profile of hepatocellular carcinoma revealed by array-based comparative genomic hybridization: identification of genetic indicators to predict patient outcome. J Hepatol 2005, 43(5):863-874.
55. Kusano N., Okita K., Shirahashi H., et al. Chromosomal imbalances detected by comparative genomic hybridization are associated with outcome of patients with hepatocellular carcinoma. Cancer 2002, 94(3):746-751.
56. Itano O., Ueda M., Kikuchi K., et al. A new predictive factor for hepatocellular carcinoma based on two-dimensional electrophoresis of genomic DNA. Oncogene 2000, 19(13):1676-1683.
57. Knudson A.G. Genetics and etiology of human cancer. Adv Hum Genet 1977, 8:1-66.
58. Marsh J.W., Finkelstein S.D., Demetris A.J., et al. Genotyping of hepatocellular carcinoma in liver transplant recipients adds predictive power for determining recurrence-free survival. Liver Transpl 2003, 9(7):664-671.
59. Macdonald G.A., Greenson J.K., Saito K., Cherian S.P., Appelman H.D., Boland C.R. Microsatellite instability and loss of heterozygosity at DNA mismatch repair gene loci occurs during hepatic carcinogenesis. Hepatology 1998, 28(1):90-97.
60. Yamamoto H., Itoh F., Fukushima H., et al. Infrequent widespread microsatellite instability in hepatocellular carcinomas. Int J Oncol 2000, 16(3):543-547.
61. Chiappini F., Gross-Goupil M., Saffroy R., et al. Microsatellite instability mutator phenotype in hepatocellular carcinoma in non-alcoholic and non-virally infected normal livers. Carcinogenesis 2004, 25(4):541-547.
62. Chao Y., Shih Y.L., Chiu J.H., et al. Overexpression of cyclin A but not Skp 2 correlates with the tumor relapse of human hepatocellular carcinoma. Cancer Res 1998, 58(5):985-990.
63. Ohashi R., Gao C., Miyazaki M., et al. Enhanced expression of cyclin E and cyclin A in human hepatocellular carcinomas. Anticancer Res 2001, 21(1B):657-662.
64. Tannapfel A., Anhalt K., Hausermann P., et al. Identification of novel proteins associated with hepatocellular carcinomas using protein microarrays. J Pathol 2003, 201(2):238-249.
65. Li X., Hui A.-M., Sun L., et al. p16INK4A hypermethylation is associated with hepatitis virus infection, age, and gender in hepatocellular carcinoma. Clin Cancer Res 2004, 10(22):7484-7489.
66. Weihrauch M., Benicke M., Lehnert G., Wittekind C., Wrbitzky R., Tannapfel A. Frequent k-ras-2 mutations and p16(INK4A)methylation in hepatocellular carcinomas in workers exposed to vinyl chloride. Br J Cancer 2001, 84(7):982-989.
67. Matsuda Y. Molecular mechanism underlying the functional loss of cyclindependent kinase inhibitors p16 and p27 in hepatocellular carcinoma. World J Gastroenterol 2008, 14(11):1734-1740.
68. Wong I.H., Lo Y.M., Yeo W., Lau W.Y., Johnson P.J. Frequent p15 promoter methylation in tumor and peripheral blood from hepatocellular carcinoma patients. Clin Cancer Res 2000, 6(9):3516-3521.
69. Morishita A., Masaki T., Yoshiji H., et al. Reduced expression of cell cycle regulator p18(INK4C) in human hepatocellular carcinoma. Hepatology 2004, 40(3):677-686.
70. Fiorentino M., Altimari A., D'Errico A., et al. Acquired expression of p27 is a favorable prognostic indicator in patients with hepatocellular carcinoma. Clin Cancer Res 2000, 6(10):3966-3972.
71. Ito Y., Matsuura N., Sakon M., et al. Expression and prognostic roles of the G1-S modulators in hepatocellular carcinoma: p27 independently predicts the recurrence. Hepatology 1999, 30(1):90-99.
72. Tannapfel A., Grund D., Katalinic A., et al. Decreased expression of p27 protein is associated with advanced tumor stage in hepatocellular carcinoma. Int J Cancer 2000, 89(4):350-355.
73. Cui J., Dong B.W., Liang P., Yu X.L., Yu D.J. Construction and clinical significance of a predictive system for prognosis of hepatocellular carcinoma. World J Gastroenterol 2005, 11(20):3027-3033.
74. Wong N., Yeo W., Wong W., et al. TOP2A overexpression in hepatocellular carcinoma correlates with early age onset, shorter patients survival and chemoresistance. Int J Cancer 2009, 124(3):644-652.
75. Ito Y., Miyoshi E., Takeda T., et al. Expression and possible role of ets-1 in hepatocellular carcinoma. Am J Clin Pathol 2000, 114(5):719-725.
76. Garcia E.J., Lawson D., Cotsonis G., Cohen C. Hepatocellular carcinoma and markers of apoptosis (bcl-2, bax, bcl-x): prognostic significance. Appl Immunohistochem Mol Morphol 2002, 10(3):210-217.
77. Watanabe J., Kushihata F., Honda K., et al. Prognostic significance of Bcl-xL in human hepatocellular carcinoma. Surgery 2004, 135(6):604-612.
78. Ito Y., Monden M., Takeda T., et al. The status of Fas and Fas ligand expression can predict recurrence of hepatocellular carcinoma. Br J Cancer 2000, 82(6):1211-1217.
79. Gao Q., Wang X.Y., Qiu S.J., et al. Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma. Clin Cancer Res 2009, 15(3):971-979.
80. Fields A.C., Cotsonis G., Sexton D., Santoianni R., Cohen C. Survivin expression in hepatocellular carcinoma: correlation with proliferation, prognostic parameters, and outcome. Mod Pathol 2004, 17(11):1378-1385.
81. Ikeguchi M., Ueda T., Sakatani T., Hirooka Y., Kaibara N. Expression of survivin messenger RNA correlates with poor prognosis in patients with hepatocellular carcinoma. Diagn Mol Pathol 2002, 11(1):33-40.
82. Chen C.-J., Kyo S., Liu Y.-C., et al. Modulation of human telomerase reverse transcriptase in hepatocellular carcinoma. World J Gastroenterol 2004, 10(5):638-642.
83. Kishimoto K., Fujimoto J., Takeuchi M., Yamamoto H., Ueki T., Okamoto E. Telomerase activity in hepatocellular carcinoma and adjacent liver tissues. J Surg Oncol 1998, 69(3):119-124.
84. Kobayashi T., Kubota K., Takayama T., Makuuchi M. Telomerase activity as a predictive marker for recurrence of hepatocellular carcinoma after hepatectomy. Am J Surg 2001, 181(3):284-288.
85. Tatsuma T., Goto S., Kitano S., Lin Y.C., Lee C.M., Chen C.L. Telomerase activity in peripheral blood for diagnosis of hepatoma. J Gastroenterol Hepatol 2000, 15(9):1064-1070.
86. Nelson W.J., Nusse R. Convergence of Wnt, beta-catenin, and cadherin pathways. Science 2004, 303(5663):1483-1487.
87. Aravalli R.N., Steer C.J., Cressman E.N. Molecular mechanisms of hepatocellular carcinoma. Hepatology 2008, 48(6):2047-2063.
88. Endo K., Ueda T., Ueyama J., Ohta T., Terada T. Immunoreactive E-cadherin, alpha-catenin, beta-catenin, and gamma-catenin proteins in hepatocellular carcinoma: relationships with tumor grade, clinicopathologic parameters, and patients' survival. Hum Pathol 2000, 31(5):558-565.
89. Inagawa S., Itabashi M., Adachi S., et al. Expression and prognostic roles of beta-catenin in hepatocellular carcinoma: correlation with tumor progression and postoperative survival. Clin Cancer Res 2002, 8(2):450-456.
90. Soyama A., Eguchi S., Takatsuki M., et al. Significance of the serum level of soluble E-cadherin in patients with HCC. Hepatogastroenterology 2008, 55(85):1390-1393.
91. Hsu H.C., Jeng Y.M., Mao T.L., Chu J.S., Lai P.L., Peng S.Y. Beta-catenin mutations are associated with a subset of low-stage hepatocellular carcinoma negative for hepatitis B virus and with favorable prognosis. Am J Pathol 2000, 157(3):763-770.
92. Wong C.M., Fan S.T., Ng I.O. Beta-catenin mutation and overexpression in hepatocellular carcinoma: clinicopathologic and prognostic significance. Cancer 2001, 92(1):136-145.
93. Lee H.H., Uen Y.H., Tian Y.F., et al. Wnt-1 protein as a prognostic biomarker for hepatitis B-related and hepatitis C-related hepatocellular carcinoma after surgery. Cancer Epidemiol Biomarkers Prev 2009, 18(5):1562-1569.
94. Zhai B., Yan H.X., Liu S.Q., Chen L., Wu M.C., Wang H.Y. Reduced expression of E-cadherin/catenin complex in hepatocellular carcinomas. World J Gastroenterol 2008, 14(37):5665-5673.
95. Korita P.V., Wakai T., Shirai Y., et al. Overexpression of osteopontin independently correlates with vascular invasion and poor prognosis in patients with hepatocellular carcinoma. Hum Pathol 2008, 39(12):1777-1783.
96. Goodison S., Urquidi V., Tarin D. CD44 cell adhesion molecules. Mol Pathol 1999, 52(4):189-196.
97. Endo K., Terada T. Protein expression of CD44 (standard and variant isoforms) in hepatocellular carcinoma: relationships with tumor grade, clinicopathologic parameters, p53 expression, and patient survival. J Hepatol 2000, 32(1):78-84.
98. Yang G.H., Fan J., Xu Y., et al. Osteopontin combined with CD44, a novel prognostic biomarker for patients with hepatocellular carcinoma undergoing curative resection. Oncologist 2008, 13(11):1155-1165.
99. Mei M.H., Xu J., Shi Q.F., Yang J.H., Chen Q., Qin L.L. Clinical significance of serum intercellular adhesion molecule-1 detection in patients with hepatocellular carcinoma. World J Gastroenterol 2000, 6(3):408-410.
100. Fritz G., Brachetti C., Bahlmann F., Schmidt M., Kaina B. Rho GTPases in human breast tumours: expression and mutation analyses and correlation with clinical parameters. Br J Cancer 2002, 87(6):635-644.
101. Suwa H., Ohshio G., Imamura T., et al. Overexpression of the rhoC gene correlates with progression of ductal adenocarcinoma of the pancreas. Br J Cancer 1998, 77(1):147-152.
102. Horiuchi A., Imai T., Wang C., et al. Up-regulation of small GTPases, RhoA and RhoC, is associated with tumor progression in ovarian carcinoma. Lab Invest 2003, 83(6):861-870.
103. Wang W., Yang L.Y., Huang G.W., et al. Genomic analysis reveals RhoC as a potential marker in hepatocellular carcinoma with poor prognosis. Br J Cancer 2004, 90(12):2349-2355.
104. Xiaorong L., Wei W., Liyuan Q., Kaiyan Y. Underexpression of deleted in liver cancer 2 (DLC2) is associated with overexpression of RhoA and poor prognosis in hepatocellular carcinoma. BMC Cancer 2008, 8:205.
105. Moseley J.B., Bartolini F., Okada K., Wen Y., Gundersen G.G., Goode B.L. Regulated binding of adenomatous polyposis coli protein to actin. J Biol Chem 2007, 282(17):12661-12668.
106. Orimo T., Ojima H., Hiraoka N., et al. Proteomic profiling reveals the prognostic value of adenomatous polyposis coli-end-binding protein 1 in hepatocellular carcinoma. Hepatology 2008, 48(6):1851-1863.
107. Theret N., Musso O., Turlin B., et al. Increased extracellular matrix remodeling is associated with tumor progression in human hepatocellular carcinomas. Hepatology 2001, 34(1):82-88.
108. Yamamoto H., Itoh F., Adachi Y., et al. Relation of enhanced secretion of active matrix metalloproteinases with tumor spread in human hepatocellular carcinoma. Gastroenterology 1997, 112(4):1290-1296.
109. Korn W.M. Moving toward an understanding of the metastatic process in hepatocellular carcinoma. World J Gastroenterol 2001, 7(6):777-778.
110. Gorrin Rivas M.J., Arii S., Furutani M., et al. Expression of human macrophage metalloelastase gene in hepatocellular carcinoma: correlation with angiostatin generation and its clinical significance. Hepatology 1998, 28(4):986-993.
111. Itoh T., Shiro T., Seki T., et al. Relationship between p53 overexpression and the proliferative activity in hepatocellular carcinoma. Int J Mol Med 2000, 6(2):137-142.
112. Zheng Q., Tang Z.Y., Xue Q., Shi D.R., Song H.Y., Tang H.B. Invasion and metastasis of hepatocellular carcinoma in relation to urokinase-type plasminogen activator, its receptor and inhibitor. J Cancer Res Clin Oncol 2000, 126(11):641-646.
113. Jiang Y.F., Yang Z.H., Hu J.Q. Recurrence or metastasis of HCC:predictors, early detection and experimental antiangiogenic therapy. World J Gastroenterol 2000, 6(1):61-65.
114. Morinaga S., Imada T., Shimizu A., et al. Angiogenesis in hepatocellular carcinoma as evaluated by alpha smooth muscle actin immunohistochemistry. Hepatogastroenterology 2001, 48(37):224-228.
115. Poon R.T., Ng I.O., Lau C., et al. Tumor microvessel density as a predictor of recurrence after resection of hepatocellular carcinoma: a prospective study. J Clin Oncol 2002, 20(7):1775-1785.
116. Ho J.W., Poon R.T., Sun C.K., Xue W.C., Fan S.T. Clinicopathological and prognostic implications of endoglin (CD105) expression in hepatocellular carcinoma and its adjacent non-tumorous liver. World J Gastroenterol 2005, 11(2):176-181.
117. El-Assal O.N., Yamanoi A., Soda Y., et al. Clinical significance of microvessel density and vascular endothelial growth factor expression in hepatocellular carcinoma and surrounding liver: possible involvement of vascular endothelial growth factor in the angiogenesis of cirrhotic liver. Hepatology 1998, 27(6):1554-1562.
118. Jeng K.S., Sheen I.S., Wang Y.C., et al. Is the vascular endothelial growth factor messenger RNA expression in resectable hepatocellular carcinoma of prognostic value after resection?. World J Gastroenterol 2004, 10(5):676-681.
119. Poon R.T., Ho J.W., Tong C.S., Lau C., Ng I.O., Fan S.T. Prognostic significance of serum vascular endothelial growth factor and endostatin in patients with hepatocellular carcinoma. Br J Surg 2004, 91(10):1354-1360.
120. Chao Y., Li C.P., Chau G.Y., et al. Prognostic significance of vascular endothelial growth factor, basic fibroblast growth factor, and angiogenin in patients with resectable hepatocellular carcinoma after surgery. Ann Surg Oncol 2003, 10(4):355-362.
121. Jia J.B., Zhuang P.Y., Sun H.C., et al. Protein expression profiling of vascular endothelial growth factor and its receptors identifies subclasses of hepatocellular carcinoma and predicts survival. J Cancer Res Clin Oncol 2009, 135(6):847-854.
122. Zhou J., Tang Z.Y., Fan J., et al. Expression of platelet-derived endothelial cell growth factor and vascular endothelial growth factor in hepatocellular carcinoma and portal vein tumor thrombus. J Cancer Res Clin Oncol 2000, 126(1):57-61.
123. Ezaki T., Ikegami T., Maeda T., et al. Prognostic value of thymidine phosphorylase activity in liver tissue adjacent to hepatocellular carcinoma. Int J Clin Oncol 2005, 10(3):171-176.
124. Hu J., Xu Y., Shen Z.Z., et al. High expressions of vascular endothelial growth factor and platelet-derived endothelial cell growth factor predict poor prognosis in alpha-fetoprotein-negative hepatocellular carcinoma patients after curative resection. J Cancer Res Clin Oncol 2009, 135(10):1359-1367.
125. Wada H., Nagano H., Yamamoto H., et al. Expression pattern of angiogenic factors and prognosis after hepatic resection in hepatocellular carcinoma: importance of angiopoietin-2 and hypoxia-induced factor-1 alpha. Liver Int 2006, 26(4):414-423.
126. Ikeguchi M., Ueta T., Yamane Y., Hirooka Y., Kaibara N. Inducible nitric oxide synthase and survivin messenger RNA expression in hepatocellular carcinoma. Clin Cancer Res 2002, 8(10):3131-3136.
127. Rahman M.A., Dhar D.K., Yamaguchi E., et al. Coexpression of inducible nitric oxide synthase and COX-2 in hepatocellular carcinoma and surrounding liver: possible involvement of COX-2 in the angiogenesis of hepatitis C virus-positive cases. Clin Cancer Res 2001, 7(5):1325-1332.
128. Poon R.T., Ng I.O., Lau C., Yu W.C., Fan S.T., Wong J. Correlation of serum basic fibroblast growth factor levels with clinicopathologic features and postoperative recurrence in hepatocellular carcinoma. Am J Surg 2001, 182(3):298-304.
129. Kaido T., Oe H., Yoshikawa A., Mori A., Arii S., Imamura M. Tissue factor is a useful prognostic factor of recurrence in hepatocellular carcinoma in 5-year survivors. Hepatogastroenterology 2005, 52(65):1383-1387.
130. Hu T.H., Huang C.C., Wu C.L., et al. Increased endostatin/collagen XVIII expression correlates with elevated VEGF level and poor prognosis in hepatocellular carcinoma. Mod Pathol 2005, 18(5):663-672.
131. Strieter R.M., Kunkel S.L., Elner V.M., et al. Interleukin-8. A corneal factor that induces neovascularization. Am J Pathol 1992, 141(6):1279-1284.
132. Luca M., Huang S., Gershenwald J.E., Singh R.K., Reich R., Bar-Eli M. Expression of interleukin-8 by human melanoma cells up-regulates MMP-2 activity and increases tumor growth and metastasis. Am J Pathol 1997, 151(4):1105-1113.
133. Ren Y., Poon R.T., Tsui H.T., et al. Interleukin-8 serum levels in patients with hepatocellular carcinoma: correlations with clinicopathological features and prognosis. Clin Cancer Res 2003, 9(16 Pt 1):5996-6001.
134. Akiba J., Yano H., Ogasawara S., Higaki K., Kojiro M. Expression and function of interleukin-8 in human hepatocellular carcinoma. Int J Oncol 2001, 18(2):257-264.
135. Kubo F., Ueno S., Hiwatashi K., et al. Interleukin 8 in human hepatocellular carcinoma correlates with cancer cell invasion of vessels but not with tumor angiogenesis. Ann Surg Oncol 2005, 12(10):800-807.
136. Mitsuhashi N., Shimizu H., Ohtsuka M., et al. Angiopoietins and Tie-2 expression in angiogenesis and proliferation of human hepatocellular carcinoma. Hepatology 2003, 37(5):1105-1113.
137. Okumoto K., Hattori E., Tamura K., et al. Possible contribution of circulating transforming growth factor-beta1 to immunity and prognosis in unresectable hepatocellular carcinoma. Liver Int 2004, 24(1):21-28.
138. Ikeguchi M., Iwamoto A., Taniguchi K., Katano K., Hirooka Y. The gene expression level of transforming growth factor-beta (TGF-beta) as a biological prognostic marker of hepatocellular carcinoma. J Exp Clin Cancer Res 2005, 24(3):415-421.
139. Song B.C., Chung Y.H., Kim J.A., et al. Transforming growth factor-beta1 as a useful serologic marker of small hepatocellular carcinoma. Cancer 2002, 94(1):175-180.
140. Zhou L., Liu J., Luo F. Serum tumor markers for detection of hepatocellular carcinoma. World J Gastroenterol 2006, 12(8):1175-1181.
141. Tsai J.F., Jeng J.E., Chuang L.Y., et al. Elevated urinary transforming growth factor-beta1 level as a tumour marker and predictor of poor survival in cirrhotic hepatocellular carcinoma. Br J Cancer 1997, 76(2):244-250.
142. Ito Y., Takeda T., Sakon M., et al. Expression and clinical significance of erb-B receptor family in hepatocellular carcinoma. Br J Cancer 2001, 84(10):1377-1383.
143. Osada S., Kanematsu M., Imai H., Goshima S. Clinical significance of serum HGF and c-Met expression in tumor tissue for evaluation of properties and treatment of hepatocellular carcinoma. Hepatogastroenterology 2008, 55(82-83):544-549.
144. Soresi M., Magliarisi C., Campagna P., et al. Usefulness of alpha-fetoprotein in the diagnosis of hepatocellular carcinoma. Anticancer Res 2003, 23(2C):1747-1753.
145. Tangkijvanich P., Anukulkarnkusol N., Suwangool P., et al. Clinical characteristics and prognosis of hepatocellular carcinoma: analysis based on serum alpha-fetoprotein levels. J Clin Gastroenterol 2000, 31(4):302-308.
146. Fujioka M., Nakashima Y., Nakashima O., Kojiro M. Immunohistologic study on the expressions of alpha-fetoprotein and protein induced by vitamin K absence or antagonist II in surgically resected small hepatocellular carcinoma. Hepatology 2001, 34(6):1128-1134.
147. Iida H., Honda M., Kawai H.F., et al. Ephrin-A1 expression contributes to the malignant characteristics of {alpha}-fetoprotein producing hepatocellular carcinoma. Gut 2005, 54(6):843-851.
148. Khien V.V., Mao H.V., Chinh T.T., et al. Clinical evaluation of lentil lectin-reactive alpha-fetoprotein-L3 in histology-proven hepatocellular carcinoma. Int J Biol Markers 2001, 16(2):105-111.
149. Oka H., Saito A., Ito K., Kumada T., et al. Multicenter prospective analysis of newly diagnosed hepatocellular carcinoma with respect to the percentage of Lens culinaris agglutinin-reactive alpha-fetoprotein. J Gastroenterol Hepatol 2001, 16(12):1378-1383.
150. Nassar A., Cohen C., Siddiqui M.T. Utility of glypican-3 and survivin in differentiating hepatocellular carcinoma from benign and preneoplastic hepatic lesions and metastatic carcinomas in liver fine-needle aspiration biopsies. Diagn Cytopathol 2009, 37(9):629-635.
151. Capurro M., Wanless I.R., Sherman M., et al. Glypican-3: a novel serum and histochemical marker for hepatocellular carcinoma. Gastroenterology 2003, 125(1):89-97.
152. Nakatsura T., Yoshitake Y., Senju S., et al. Glypican-3, overexpressed specifically in human hepatocellular carcinoma, is a novel tumor marker. Biochem Biophys Res Commun 2003, 306(1):16-25.
153. Hippo Y., Watanabe K., Watanabe A., et al. Identification of soluble NH2-terminal fragment of glypican-3 as a serological marker for early-stage hepatocellular carcinoma. Cancer Res 2004, 64(7):2418-2423.
154. Shirakawa H., Suzuki H., Shimomura M., et al. Glypican-3 expression is correlated with poor prognosis in hepatocellular carcinoma. Cancer Sci 2009, 100(8):1403-1407.
155. Cui R., He J., Zhang F., et al. Diagnostic value of protein induced by vitamin K absence (PIVKAII) and hepatoma-specific band of serum gamma-glutamyl transferase (GGTII) as hepatocellular carcinoma markers complementary to alpha-fetoprotein. Br J Cancer 2003, 88(12):1878-1882.
156. Tangkijvanich P., Tosukhowong P., Bunyongyod P., et al. Alpha-l-fucosidase as a serum marker of hepatocellular carcinoma in Thailand. Southeast Asian J Trop Med Public Health 1999, 30(1):110-114.
157. Ishizuka H., Nakayama T., Matsuoka S., et al. Prediction of the development of hepato-cellular-carcinoma in patients with liver cirrhosis by the serial determinations of serum alpha-l-fucosidase activity. Intern Med 1999, 38(12):927-931.
158. Suzuki M., Shiraha H., Fujikawa T., et al. Des-gamma-carboxy prothrombin is a potential autologous growth factor for hepatocellular carcinoma. J Biol Chem 2005, 280(8):6409-6415.
159. Cui R., Wang B., Ding H., Shen H., Li Y., Chen X. Usefulness of determining a protein induced by vitamin K absence in detection of hepatocellular carcinoma. Chin Med J (Engl) 2002, 115(1):42-45.
160. Marrero J.A., Su G.L., Wei W., et al. Des-gamma carboxyprothrombin can differentiate hepatocellular carcinoma from nonmalignant chronic liver disease in American patients. Hepatology 2003, 37(5):1114-1121.
161. Shimizu A., Shiraki K., Ito T., et al. Sequential fluctuation pattern of serum des-gamma-carboxy prothrombin levels detected by high-sensitive electrochemiluminescence system as an early predictive marker for hepatocellular carcinoma in patients with cirrhosis. Int J Mol Med 2002, 9(3):245-250.
162. Hamamura K., Shiratori Y., Shiina S., et al. Unique clinical characteristics of patients with hepatocellular carcinoma who present with high plasma des-gamma-carboxy prothrombin and low serum alpha-fetoprotein. Cancer 2000, 88(7):1557-1564.
163. Okuda H., Nakanishi T., Takatsu K., et al. Comparison of clinicopathological features of patients with hepatocellular carcinoma seropositive for alpha-fetoprotein alone and those seropositive for des-gamma-carboxy prothrombin alone. J Gastroenterol Hepatol 2001, 16(11):1290-1296.
164. Kim H.S., Park J.W., Jang J.S., et al. Prognostic values of alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II in hepatitis B virus-related hepatocellular carcinoma: a prospective study. J Clin Gastroenterol 2009, 43(5):482-488.
165. Tang W., Kokudo N., Sugawara Y., et al. Des-gamma-carboxyprothrombin expression in cancer and/or non-cancer liver tissues: association with survival of patients with resectable hepatocellular carcinoma. Oncol Rep 2005, 13(1):25-30.
166. Harino Y., Fujii M., Imura S., et al. The role of des-gamma-carboxyprothrombin expression in hepatocellular carcinoma. Hepatogastroenterology 2008, 55(85):1385-1389.
167. Kobayashi M., Ikeda K., Kawamura Y., et al. High serum des-gamma-carboxy prothrombin level predicts poor prognosis after radiofrequency ablation of hepatocellular carcinoma. Cancer 2009, 115(3):571-580.
168. Marrero J.A., Romano P.R., Nikolaeva O., et al. GP73, a resident Golgi glycoprotein, is a novel serum marker for hepatocellular carcinoma. J Hepatol 2005, 43(6):1007-1012.
169. Riener M.O., Stenner F., Liewen H., et al. Golgi phosphoprotein 2 (GOLPH2) expression in liver tumors and its value as a serum marker in hepatocellular carcinomas. Hepatology 2009, 49(5):1602-1609.
170. Matsumura M., Niwa Y., Kato N., et al. Detection of alpha-fetoprotein mRNA, an indicator of hematogenous spreading hepatocellular carcinoma, in the circulation: a possible predictor of metastatic hepatocellular carcinoma. Hepatology 1994, 20(6):1418-1425.
171. Ijichi M., Takayama T., Matsumura M., Shiratori Y., Omata M., Makuuchi M. Alpha-fetoprotein mRNA in the circulation as a predictor of postsurgical recurrence of hepatocellular carcinoma: a prospective study. Hepatology 2002, 35(4):853-860.
172. Jeng K.S., Sheen I.S., Tsai Y.C. Circulating messenger RNA of alpha-fetoprotein: a possible risk factor of recurrence after resection of hepatocellular carcinoma. Arch Surg 2004, 139(10):1055-1060.
173. Ding X., Yang L.Y., Huang G.W., et al. Role of AFP mRNA expression in peripheral blood as a predictor for postsurgical recurrence of hepatocellular carcinoma: a systematic review and meta-analysis. World J Gastroenterol 2005, 11(17):2656-2661.
174. Sheen I.S., Jeng K.S., Tsai Y.C. Is the expression of gamma-glutamyl transpeptidase messenger RNA an indicator of biological behavior in recurrent hepatocellular carcinoma?. World J Gastroenterol 2003, 9(3):468-473.
175. Tsutsumi M., Sakamuro D., Takada A., Zang S.C., Furukawa T., Taniguchi N. Detection of a unique gamma-glutamyl transpeptidase messenger RNA species closely related to the development of hepatocellular carcinoma in humans: a new candidate for early diagnosis of hepatocellular carcinoma. Hepatology 1996, 23(5):1093-1097.
176. Himoto T., Kuriyama S., Zhang J.Y., et al. Analyses of autoantibodies against tumor-associated antigens in patients with hepatocellular carcinoma. Int J Oncol 2005, 27(4):1079-1085.
177. Tsai J.F., Jeng J.E., Chuang L.Y., et al. Serum insulin-like growth factor-II as a serologic marker of small hepatocellular carcinoma. Scand J Gastroenterol 2005, 40(1):68-75.
178. Cheung S.T., Fan S.T., Lee Y.T., et al. Albumin mRNA in plasma predicts post-transplant recurrence of patients with hepatocellular carcinoma. Transplantation 2008, 85(1):81-87.
179. Miura N., Maeda Y., Kanbe T., et al. Serum human telomerase reverse transcriptase messenger RNA as a novel tumor marker for hepatocellular carcinoma. Clin Cancer Res 2005, 11(9):3205-3209.
180. Kong S.Y., Park J.W., Kim J.O., et al. Alpha-fetoprotein and human telomerase reverse transcriptase mRNA levels in peripheral blood of patients with hepatocellular carcinoma. J Cancer Res Clin Oncol 2009, 135(8):1091-1098.
181. Mou D.C., Cai S.L., Peng J.R., et al. Evaluation of MAGE-1 and MAGE-3 as tumour-specific markers to detect blood dissemination of hepatocellular carcinoma cells. Br J Cancer 2002, 86(1):110-116.
182. Yoon S.K., Lim N.K., Ha S.A., et al. The human cervical cancer oncogene protein is a biomarker for human hepatocellular carcinoma. Cancer Res 2004, 64(15):5434-5441.
183. Cheung S.T., Wong S.Y., Leung K.L., et al. Granulin-epithelin precursor overexpression promotes growth and invasion of hepatocellular carcinoma. Clin Cancer Res 2004, 10(22):7629-7636.
184. Tricoli J.V., Jacobson J.W. MicroRNA: potential for cancer detection, diagnosis, and prognosis. Cancer Res 2007, 67(10):4553-4555.
185. Yamamoto Y., Kosaka N., Tanaka M., et al. MicroRNA-500 as a potential diagnostic marker for hepatocellular carcinoma. Biomarkers 2009, 14(7):529-538.
186. Xiong Y., Fang J.H., Yun J.P., et al. Effects of MicroRNA-29 on apoptosis, tumorigenicity, and prognosis of hepatocellular carcinoma. Hepatology 2009.
187. Murakami Y., Yasuda T., Saigo K., et al. Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene 2006, 25(17):2537-2545.
188. Budhu A., Jia H.L., Forgues M., et al. Identification of metastasis-related microRNAs in hepatocellular carcinoma. Hepatology 2008, 47(3):897-907.
189. Jiang J., Gusev Y., Aderca I., et al. Association of MicroRNA expression in hepatocellular carcinomas with hepatitis infection, cirrhosis, and patient survival. Clin Cancer Res 2008, 14(2):419-427.
190. Meng F., Henson R., Wehbe-Janek H., Ghoshal K., Jacob S.T., Patel T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 2007, 133(2):647-658.
191. Wang Y., Lee A.T., Ma J.Z., et al. Profiling microRNA expression in hepatocellular carcinoma reveals microRNA-224 up-regulation and apoptosis inhibitor-5 as a microRNA-224-specific target. J Biol Chem 2008, 283(19):13205-13215.
192. Fornari F., Gramantieri L., Ferracin M., et al. MiR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma. Oncogene 2008, 27(43):5651-5661.
193. Gramantieri L., Fornari F., Ferracin M., et al. MicroRNA-221 targets Bmf in hepatocellular carcinoma and correlates with tumor multifocality. Clin Cancer Res 2009, 15(16):5073-5081.
194. Wong Q.W., Lung R.W., Law P.T., et al. MicroRNA-223 is commonly repressed in hepatocellular carcinoma and potentiates expression of Stathmin 1. Gastroenterology 2008, 135(1):257-269.
195. Li W., Xie L., He X., et al. Diagnostic and prognostic implications of microRNAs in human hepatocellular carcinoma. Int J Cancer 2008, 123(7):1616-1622.
196. Fornari F., Gramantieri L., Giovannini C., et al. MiR-122/cyclin G1 interaction modulates p53 activity and affects doxorubicin sensitivity of human hepatocarcinoma cells. Cancer Res 2009, 69(14):5761-5767.
197. Lin C.J., Gong H.Y., Tseng H.C., Wang W.L., Wu J.L. miR-122 targets an anti-apoptotic gene, Bcl-w, in human hepatocellular carcinoma cell lines. Biochem Biophys Res Commun 2008, 375(3):315-320.
198. Coulouarn C., Factor V.M., Andersen J.B., Durkin M.E., Thorgeirsson S.S. Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties. Oncogene 2009, 28(40):3526-3536.
199. Li N., Fu H., Tie Y., et al. miR-34a inhibits migration and invasion by down-regulation of c-Met expression in human hepatocellular carcinoma cells. Cancer Lett 2009, 275(1):44-53.
200. Liu W.H., Yeh S.H., et al. MicroRNA-18a prevents estrogen receptor-alpha expression, promoting proliferation of hepatocellular carcinoma cells. Gastroenterology 2009, 136(2):683-693.
201. Li S., Fu H., Wang Y., et al. MicroRNA-101 regulates expression of the v-fos FBJ murine osteosarcoma viral oncogene homolog (FOS) oncogene in human hepatocellular carcinoma. Hepatology 2009, 49(4):1194-1202.
202. Xu T., Zhu Y., Xiong Y., Ge Y.Y., Yun J.P., Zhuang S.M. MicroRNA-195 suppresses tumorigenicity and regulates G1/S transition of human hepatocellular carcinoma cells. Hepatology 2009, 50(1):113-121.
203. Zhang X., Liu S., Hu T., He Y., Sun S. Up-regulated microRNA-143 transcribed by nuclear factor kappa B enhances hepatocarcinoma metastasis by repressing fibronectin expression. Hepatology 2009, 50(2):490-499.
204. Huang X.H., Wang Q., Chen J.S., et al. Bead-based microarray analysis of microRNA expression in hepatocellular carcinoma: miR-338 is downregulated. Hepatol Res 2009, 39(8):786-794.
205. Salvi A., Sabelli C., Moncini S., et al. MicroRNA-23b mediates urokinase and c-met downmodulation and a decreased migration of human hepatocellular carcinoma cells. FEBS J 2009, 276(11):2966-2982.
206. Kota J., Chivukula R.R., O'Donnell K.A., et al. Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell 2009, 137(6):1005-1017.
207. Gao Y., He Y., Ding J., et al. An insertion/deletion polymorphism at miRNA-122-binding site in the interleukin-1alpha 3' untranslated region confers risk for hepatocellular carcinoma. Carcinogenesis 2009, 30(12):2064-2069.
208. Chung G.E., Yoon J.H., Myung S.J., et al. High expression of microRNA-15b predicts a low risk of tumor recurrence following curative resection of hepatocellular carcinoma. Oncol Rep 2010, 23(1):113-119.
209. Nakano S., Haratake J., Okamoto K., Takeda S. Investigation of resected multinodular hepatocellular carcinoma: assessment of unicentric or multicentric genesis from histological and prognostic viewpoint. Am J Gastroenterol 1994, 89(2):189-193.
210. Wilkens L., Bredt M., Flemming P., Klempnauer J., Heinrich Kreipe H. Differentiation of multicentric origin from intra-organ metastatic spread of hepatocellular carcinomas by comparative genomic hybridization. J Pathol 2000, 192(1):43-51.
211. Ng I.O., Guan X.Y., Poon R.T., Fan S.T., Lee J.M.F. Determination of the molecular relationship between multiple tumour nodules in hepatocellular carcinoma differentiates multicentric origin from intrahepatic metastasis. J Pathol 2003, 199(3):345-353.
212. Potti A., Dressman H.K., Bild A., et al. Genomic signatures to guide the use of chemotherapeutics. Nat Med 2006, 12(11):1294-1300.
213. Tanaka S., Arii S. Molecularly targeted therapy for hepatocellular carcinoma. Cancer Sci 2009, 100:1-8.
214. Llovet J.M., Bruix J. Molecular targeted therapies in hepatocellular carcinoma. Hepatology 2008, 48:1312-1327.
215. Zhu A.X., Duda D.G., Sahani D.V., Jain R.K. HCC and angiogenesis: possible targets and future directions. Nat Rev Clin Oncol 2011.
216. Abou-Alfa G.K., Schwartz L., Ricci S., et al. Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol 2006, 24:4293-4300.
217. Llovet J.M., Ricci S., Mazzaferro V., et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008, 359(4):378-390.
218. Cheng A.L., Kang Y.K., Chen Z., et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 2009, 10:25-34.
219. Printz C. Clinical trials of note. Sorafenib as adjuvant treatment in the prevention of disease recurrence in patients with hepatocellular carcinoma (HCC) (STORM). Cancer 2009, 115(20):4646.
220. Yeganeh M., Finn R.S., Saab S. Apparent remission of a solitary metastatic pulmonary lesion in a liver transplant recipient treated with sorafenib. Am J Transplant 2009, 9(12):2851-2854.
221. Saab S., McTigue M., Finn R.S., Busuttil R.W. Sorafenib as adjuvant therapy for high-risk hepatocellular carcinoma in liver transplant recipients: feasibility and efficacy. Exp Clin Transpl 2010, 4:307-313.
222. Tanaka S., Sugimachi K., Maehara S., et al. Oncogenic signal transduction and therapeutic strategy for hepatocellular carcinoma. Surgery 2002, 131:S142-S147.
223. Wilhelm S.M., Dumas J., Adnane L., et al. Regorafenib (BAY 73-4506): A new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer 2011, 129(1):245-255.
224. Tanaka S., Arii S. Current status of molecularly targeted therapy for hepatocellular carcinoma: basic science. Int J Clin Oncol 2010, 15:235-241.