Prognostic biomarkers for prediction of recurrence of hepatocellular carcinoma: Current status and future prospects

World Journal of Gastroenterology

Volumn 20, Issue 12, 2014, Pages 3112-3124

  Lee, Seow Chong ^a   Tan, Hwee Tong ^a   Chung, Maxey Ching Ming ^a,b  

^a NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^b NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

Author keywords

Biomarker; Liver cancer; Metabolomics; Proteomics; Recurrence; Transcriptomics

Indexed keywords

ALPHA INTERFERON; HEPATOMA DERIVED GROWTH FACTOR; MICRORNA; MICRORNA 122; MICRORNA 155; MICRORNA 214; MICRORNA 29; OLIGONUCLEOTIDE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PREGNANCY SPECIFIC BETA1 GLYCOPROTEIN; PROTEIN CDC42; PROTEIN KINASE LKB1; PROTEIN MSH2; TRANSCRIPTOME; TUMOR MARKER;

ALPHA FETOPROTEIN BLOOD LEVEL; ARTICLE; BILE DUCT CARCINOMA; CANCER PROGNOSIS; CANCER RECURRENCE; DNA MICROARRAY; GENE EXPRESSION; GENE EXPRESSION PROFILING; HEPATITIS B VIRUS; HEPATITIS C VIRUS; HUMAN; LIQUID CHROMATOGRAPHY; LIVER CELL CARCINOMA; MASS SPECTROMETRY; METABOLOMICS; MICROARRAY ANALYSIS; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; OVERALL SURVIVAL; PHENOTYPE; PROTEIN EXPRESSION; PROTEOMICS; RECURRENCE FREE SURVIVAL; RECURRENCE RISK; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; TRANSCRIPTOMICS; TUMOR SUPPRESSOR GENE; TWO DIMENSIONAL ELECTROPHORESIS; BIOLOGY; CARCINOMA, HEPATOCELLULAR; COMPLICATION; GENE EXPRESSION REGULATION; HEPATITIS B; HEPATITIS C; LIVER NEOPLASMS; METABOLISM; NEOPLASM RECURRENCE, LOCAL; PROCEDURES; PROGNOSIS; TREATMENT OUTCOME;

CARCINOMA, HEPATOCELLULAR; COMPUTATIONAL BIOLOGY; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, NEOPLASTIC; HEPATITIS B; HEPATITIS C; HUMANS; LIVER NEOPLASMS; MICRORNAS; NEOPLASM RECURRENCE, LOCAL; PHENOTYPE; PROGNOSIS; PROTEOMICS; TRANSCRIPTOME; TREATMENT OUTCOME; TUMOR MARKERS, BIOLOGICAL;

EID: 84896911977     PISSN: 10079327     EISSN: 22192840     Source Type: Journal    
DOI: 10.3748/wjg.v20.i12.3112     Document Type: Article

References (69)

1. Farazi PA, DePinho RA. Hepatocellular carcinoma patho-genesis: from genes to environment. Nat Rev Cancer 2006; 6: 674-687 [PMID: 16929323]
2. Mancuso A. Management of hepatocellular carcinoma: Enlightening the gray zones. World J Hepatol 2013; 5: 302-310 [PMID: 23805354 DOI: 10.4254/wjh.v5.i6.302]
3. Tung-Ping Poon R, Fan ST, Wong J. Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma. Ann Surg 2000; 232: 10-24 [PMID: 10862190]
4. Sherman M. Recurrence of hepatocellular carcinoma. N Engl J Med 2008; 359: 2045-2047 [PMID: 18923166 DOI: 10.1056/ NEJMe0807581]
5. Poon RT, Fan ST, Ng IO, Lo CM, Liu CL, Wong J. Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma. Cancer 2000; 89: 500-507 [PMID: 10931448 DOI: 10.1002/1097-0142(2 0000801)89]
6. Tangkijvanich P, Anukulkarnkusol N, Suwangool P, Lert-maharit S, Hanvivatvong O, Kullavanijaya P, Poovorawan Y. Clinical characteristics and prognosis of hepatocellular carcinoma: analysis based on serum alpha-fetoprotein levels. J Clin Gastroenterol 2000; 31: 302-308 [PMID: 11129271]
7. Tsai TJ, Chau GY, Lui WY, Tsay SH, King KL, Loong CC, Hsia CY, Wu CW. Clinical significance of microscopic tumor venous invasion in patients with resectable hepatocellular carcinoma. Surgery 2000; 127: 603-608 [PMID: 10840353]
8. Morimoto O, Nagano H, Miyamoto A, Fujiwara Y, Kondo M, Yamamoto T, Ota H, Nakamura M, Wada H, Damdinsuren B, Marubashi S, Dono K, Umeshita K, Nakamori S, Sakon M, Monden M. Association between recurrence of hepatocellu-lar carcinoma and alpha-fetoprotein messenger RNA levels in peripheral blood. Surg Today 2005; 35: 1033-1041 [PMID: 16341483 DOI: 10.1007/s00595-005-3077-5]
9. Zulehner G, Mikula M, Schneller D, van Zijl F, Huber H, Sieghart W, Grasl-Kraupp B, Waldhör T, Peck-Radosavljevic M, Beug H, Mikulits W. Nuclear beta-catenin induces an early liver progenitor phenotype in hepatocellular carcinoma and promotes tumor recurrence. Am J Pathol 2010; 176: 472-481 [PMID: 20008139 DOI: 10.2353/ajpath.2010.090300]
10. Yin X, Li YW, Jin JJ, Zhou Y, Ren ZG, Qiu SJ, Zhang BH. The clinical and prognostic implications of pluripotent stem cell gene expression in hepatocellular carcinoma. Oncol Lett 2013; 5: 1155-1162 [PMID: 23599755 DOI: 10.3892/ol.2013.1151]
11. Hu TH, Wang CC, Huang CC, Chen CL, Hung CH, Chen CH, Wang JH, Lu SN, Lee CM, Changchien CS, Tai MH. Down-regulation of tumor suppressor gene PTEN, overex-pression of p53, plus high proliferating cell nuclear antigen index predict poor patient outcome of hepatocellular carcinoma after resection. Oncol Rep 2007; 18: 1417-1426 [PMID: 17982625]
12. Woo HG, Wang XW, Budhu A, Kim YH, Kwon SM, Tang ZY, Sun Z, Harris CC, Thorgeirsson SS. Association of TP53 mutations with stem cell-like gene expression and survival of patients with hepatocellular carcinoma. Gastroenterol-ogy 2011; 140: 1063-1070 [PMID: 21094160 DOI: 10.1053/ j.gastro.2010.11.034]
13. Yano M, Hamatani K, Eguchi H, Hirai Y, MacPhee DG, Sugino K, Dohi K, Itamoto T, Asahara T. Prognosis in patients with hepatocellular carcinoma correlates to mutations of p53 and/or hMSH2 genes. Eur J Cancer 2007; 43: 1092-1100 [PMID: 17350822]
14. Huang YH, Chen ZK, Huang KT, Li P, He B, Guo X, Zhong JQ, Zhang QY, Shi HQ, Song QT, Yu ZP, Shan YF. Decreased expression of LKB1 correlates with poor prognosis in he-patocellular carcinoma patients undergoing hepatectomy. Asian Pac J Cancer Prev 2013; 14: 1985-1988 [PMID: 23679304]
15. Kondo S, Ojima H, Tsuda H, Hashimoto J, Morizane C, Ikeda M, Ueno H, Tamura K, Shimada K, Kanai Y, Okusaka T. Clinical impact of c-Met expression and its gene amplification in hepatocellular carcinoma. Int J Clin Oncol 2013; 18: 207-213 [PMID: 22218908 DOI: 10.1007/s10147-011-0361-9]
16. Lee SJ, Lee J, Sohn I, Mao M, Kai W, Park CK, Lim HY. A survey of c-MET expression and amplification in 287 patients with hepatocellular carcinoma. Anticancer Res 2013; 33: 5179-5186 [PMID: 24222167]
17. Tannapfel A, Busse C, Weinans L, Benicke M, Katalinic A, Geissler F, Hauss J, Wittekind C. INK4a-ARF alterations and p53 mutations in hepatocellular carcinomas. Oncogene 2001; 20: 7104-7109 [PMID: 11704835 DOI: 10.1038/sj.onc.1204902]
18. Anzola M, Cuevas N, Lopez-Martinez M, Martinez de Pancorbo M, Burgos JJ. p16INK4A gene alterations are not a prognostic indicator for survival in patients with hepatocel-lular carcinoma undergoing curative hepatectomy. J Gastro-enterol Hepatol 2004; 19: 397-405 [PMID: 15012776]
19. Iizuka N, Oka M, Yamada-Okabe H, Nishida M, Maeda Y, Mori N, Takao T, Tamesa T, Tangoku A, Tabuchi H, Hama-da K, Nakayama H, Ishitsuka H, Miyamoto T, Hirabayashi A, Uchimura S, Hamamoto Y. Oligonucleotide microarray for prediction of early intrahepatic recurrence of hepatocellular carcinoma after curative resection. Lancet 2003; 361: 923-929 [PMID: 12648972]
20. Kurokawa Y, Matoba R, Takemasa I, Nagano H, Dono K, Nakamori S, Umeshita K, Sakon M, Ueno N, Oba S, Ishii S, Kato K, Monden M. Molecular-based prediction of early recurrence in hepatocellular carcinoma. J Hepatol 2004; 41: 284-291 [PMID: 15288478 DOI: 10.1016/j.jhep.2004.04.031]
21. Okamoto M, Utsunomiya T, Wakiyama S, Hashimoto M, Fukuzawa K, Ezaki T, Hanai T, Inoue H, Mori M. Specifc gene-expression profiles of noncancerous liver tissue predict the risk for multicentric occurrence of hepatocellular carcinoma in hepatitis C virus-positive patients. Ann Surg Oncol 2006; 13: 947-954 [PMID: 16788756 DOI: 10.1245/ ASO.2006.07.018]
22. Wang SM, Ooi LL, Hui KM. Identification and validation of a novel gene signature associated with the recurrence of human hepatocellular carcinoma. Clin Cancer Res 2007; 13: 6275-6283 [PMID: 17975138]
23. Hoshida Y, Villanueva A, Kobayashi M, Peix J, Chiang DY, Camargo A, Gupta S, Moore J, Wrobel MJ, Lerner J, Reich M, Chan JA, Glickman JN, Ikeda K, Hashimoto M, Watanabe G, Daidone MG, Roayaie S, Schwartz M, Thung S, Salvesen HB, Gabriel S, Mazzaferro V, Bruix J, Friedman SL, Kumada H, Llovet JM, Golub TR. Gene expression in fixed tissues and outcome in hepatocellular carcinoma. N Engl J Med 2008; 359: 1995-2004 [PMID: 18923165 DOI: 10.1056/NEJMoa0804525]
24. Somura H, Iizuka N, Tamesa T, Sakamoto K, Hamaguchi T, Tsunedomi R, Yamada-Okabe H, Sawamura M, Eramoto M, Miyamoto T, Hamamoto Y, Oka M. A three-gene predictor for early intrahepatic recurrence of hepatocellular carcinoma after curative hepatectomy. Oncol Rep 2008; 19: 489-495 [PMID: 18202799]
25. Tanaka S, Arii S, Yasen M, Mogushi K, Su NT, Zhao C, Imoto I, Eishi Y, Inazawa J, Miki Y, Tanaka H. Aurora kinase B is a predictive factor for the aggressive recurrence of he-patocellular carcinoma after curative hepatectomy. Br J Surg 2008; 95: 611-619 [PMID: 18311747 DOI: 10.1002/bjs.6011]
26. Woo HG, Park ES, Cheon JH, Kim JH, Lee JS, Park BJ, Kim W, Park SC, Chung YJ, Kim BG, Yoon JH, Lee HS, Kim CY, Yi NJ, Suh KS, Lee KU, Chu IS, Roskams T, Thorgeirsson SS, Kim YJ. Gene expression-based recurrence prediction of hepatitis B virus-related human hepatocellular carcinoma. Clin Cancer Res 2008; 14: 2056-2064 [PMID: 18381945 DOI: 10.1158/1078-0432.CCR-07-1473]
27. Yoshioka S, Takemasa I, Nagano H, Kittaka N, Noda T, Wada H, Kobayashi S, Marubashi S, Takeda Y, Umeshita K, Dono K, Matsubara K, Monden M. Molecular prediction of early recurrence after resection of hepatocellular carcinoma. Eur J Cancer 2009; 45: 881-889 [PMID: 19167881 DOI: 10.1016/j.ejca.2008.12.019]
28. Roessler S, Jia HL, Budhu A, Forgues M, Ye QH, Lee JS, Thorgeirsson SS, Sun Z, Tang ZY, Qin LX, Wang XW. A unique metastasis gene signature enables prediction of tumor relapse in early-stage hepatocellular carcinoma patients. Cancer Res 2010; 70: 10202-10212 [PMID: 21159642 DOI: 10.1158/0008-5472.CAN-10-2607]
29. Tsuchiya M, Parker JS, Kono H, Matsuda M, Fujii H, Rusyn I. Gene expression in nontumoral liver tissue and recurrence-free survival in hepatitis C virus-positive hepatocellular carcinoma. Mol Cancer 2010; 9: 74 [PMID: 20380719 DOI: 10.1186/1476-4598-9-74]
30. Weng L, Du J, Zhou Q, Cheng B, Li J, Zhang D, Ling C. Iden-tifcation of cyclin B1 and Sec62 as biomarkers for recurrence in patients with HBV-related hepatocellular carcinoma after surgical resection. Mol Cancer 2012; 11: 39 [PMID: 22682366 DOI: 10.1186/1476-4598-11-39]
31. Xieraili M, Yasen M, Mogushi K, Obulhasim G, Mayinuer A, Aihara A, Tanaka S, Mizushima H, Tanaka H, Arii S. Villin 1 is a predictive factor for the recurrence of high serum alpha-fetoprotein-associated hepatocellular carcinoma after hepa-tectomy. Cancer Sci 2012; 103: 1493-1501 [PMID: 22530999 DOI: 10.1111/j.1349-7006.2012.02315.x]
32. Tsunedomi R, Iizuka N, Yoshimura K, Iida M, Tsutsui M, Hashimoto N, Kanekiyo S, Sakamoto K, Tamesa T, Oka M. ABCB6 mRNA and DNA methylation levels serve as useful biomarkers for prediction of early intrahepatic recurrence of hepatitis C virus-related hepatocellular carcinoma. Int J Oncol 2013; 42: 1551-1559 [PMID: 23483087 DOI: 10.3892/ ijo.2013.1854]
33. Chen YJ, Yeh SH, Chen JT, Wu CC, Hsu MT, Tsai SF, Chen PJ, Lin CH. Chromosomal changes and clonality relationship between primary and recurrent hepatocellular carcinoma. Gastroenterology 2000; 119: 431-440 [PMID: 10930378]
34. Ho MC, Lin JJ, Chen CN, Chen CC, Lee H, Yang CY, Ni YH, Chang KJ, Hsu HC, Hsieh FJ, Lee PH. A gene expression profle for vascular invasion can predict the recurrence after resection of hepatocellular carcinoma: a microarray approach. Ann Surg Oncol 2006; 13: 1474-1484 [PMID: 17009164 DOI: 10.1245/s10434-006-9057-1]
35. Budhu A, Forgues M, Ye QH, Jia HL, He P, Zanetti KA, Kammula US, Chen Y, Qin LX, Tang ZY, Wang XW. Prediction of venous metastases, recurrence, and prognosis in he-patocellular carcinoma based on a unique immune response signature of the liver microenvironment. Cancer Cell 2006; 10: 99-111 [PMID: 16904609]
36. Costa FF, Le Blanc K, Brodin B. Concise review: cancer/testis antigens, stem cells, and cancer. Stem Cells 2007; 25: 707-711 [PMID: 17138959]
37. Lee JS, Heo J, Libbrecht L, Chu IS, Kaposi-Novak P, Calvisi DF, Mikaelyan A, Roberts LR, Demetris AJ, Sun Z, Nevens F, Roskams T, Thorgeirsson SS. A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells. Nat Med 2006; 12: 410-416 [PMID: 16532004]
38. Woo HG, Lee JH, Yoon JH, Kim CY, Lee HS, Jang JJ, Yi NJ, Suh KS, Lee KU, Park ES, Thorgeirsson SS, Kim YJ. Identification of a cholangiocarcinoma-like gene expression trait in hepatocellular carcinoma. Cancer Res 2010; 70: 3034-3041 [PMID: 20395200 DOI: 10.1158/0008-5472.CAN-09-2823]
39. Du Y, Su T, Ding Y, Cao G. Effects of antiviral therapy on the recurrence of hepatocellular carcinoma after curative resection or liver transplantation. Hepat Mon 2012; 12: e6031 [PMID: 23166535 DOI: 10.5812/hepatmon.6031]
40. Taylor MW, Tsukahara T, Brodsky L, Schaley J, Sanda C, Stephens MJ, McClintick JN, Edenberg HJ, Li L, Tavis JE, Howell C, Belle SH. Changes in gene expression during pe-gylated interferon and ribavirin therapy of chronic hepatitis C virus distinguish responders from nonresponders to antiviral therapy. J Virol 2007; 81: 3391-3401 [PMID: 17267482]
41. Gupta R, Kim S, Taylor MW. Suppression of ribosomal protein synthesis and protein translation factors by Peg-inter-feron alpha/ribavirin in HCV patients blood mononuclear cells (PBMC). J Transl Med 2012; 10: 54 [PMID: 22436241 DOI: 10.1186/1479-5876-10-54]
42. Honda M, Yamashita T, Yamashita T, Arai K, Sakai Y, Sakai A, Nakamura M, Mizukoshi E, Kaneko S. Peretinoin, an acyclic retinoid, improves the hepatic gene signature of chronic hepatitis C following curative therapy of hepatocellular carcinoma. BMC Cancer 2013; 13: 191 [PMID: 23587162 DOI: 10.1186/1471-2407-13-191]
43. Villanueva A, Hoshida Y, Battiston C, Tovar V, Sia D, Al-sinet C, Cornella H, Liberzon A, Kobayashi M, Kumada H, Thung SN, Bruix J, Newell P, April C, Fan JB, Roayaie S, Mazzaferro V, Schwartz ME, Llovet JM. Combining clinical, pathology, and gene expression data to predict recurrence of hepatocellular carcinoma. Gastroenterology 2011; 140: 1501-1512.e2 [PMID: 21320499 DOI: 10.1053/ j.gastro.2011.02.006]
44. Boyault S, Rickman DS, de Reyniès A, Balabaud C, Rebou-issou S, Jeannot E, Hérault A, Saric J, Belghiti J, Franco D, Bioulac-Sage P, Laurent-Puig P, Zucman-Rossi J. Transcrip-tome classifcation of HCC is related to gene alterations and to new therapeutic targets. Hepatology 2007; 45: 42-52 [PMID: 17187432 DOI: 10.1002/hep.21467]
45. Griffths-Jones S, Saini HK, van Dongen S, Enright AJ. miR-Base: tools for microRNA genomics. Nucleic Acids Res 2008; 36: D154-D158 [PMID: 17991681]
46. Wiemer EA. The role of microRNAs in cancer: no small matter. Eur J Cancer 2007; 43: 1529-1544 [PMID: 17531469]
47. Augello C, Vaira V, Caruso L, Destro A, Maggioni M, Park YN, Montorsi M, Santambrogio R, Roncalli M, Bosari S. Mi-croRNA profling of hepatocarcinogenesis identifes C19MC cluster as a novel prognostic biomarker in hepatocellular carcinoma. Liver Int 2012; 32: 772-782 [PMID: 22429613 DOI: 10.1111/j.1478-3231.2012.02795.x]
48. Shih TC, Tien YJ, Wen CJ, Yeh TS, Yu MC, Huang CH, Lee YS, Yen TC, Hsieh SY. MicroRNA-214 downregulation contributes to tumor angiogenesis by inducing secretion of the hepatoma-derived growth factor in human hepatoma. J Hepatol 2012; 57: 584-591 [PMID: 22613005 DOI: 10.1016/ j.jhep.2012.04.031]
49. Zhu HT, Dong QZ, Sheng YY, Wei JW, Wang G, Zhou HJ, Ren N, Jia HL, Ye QH, Qin LX. MicroRNA-29a-5p is a novel predictor for early recurrence of hepatitis B virus-related hepatocellular carcinoma after surgical resection. PLoS One 2012; 7: e52393 [PMID: 23285022 DOI: 10.1371/journal. pone.0052393]
50. Xia H, Ooi LL, Hui KM. MiR-214 targets β-catenin pathway to suppress invasion, stem-like traits and recurrence of human hepatocellular carcinoma. PLoS One 2012; 7: e44206 [PMID: 22962603 DOI: 10.1371/journal.pone.0044206]
51. Huang YH, Lin KH, Chen HC, Chang ML, Hsu CW, Lai MW, Chen TC, Lee WC, Tseng YH, Yeh CT. Identifcation of postoperative prognostic microRNA predictors in hepatocellular carcinoma. PLoS One 2012; 7: e37188 [PMID: 22629365 DOI: 10.1371/journal.pone.0037188]
52. Han ZB, Chen HY, Fan JW, Wu JY, Tang HM, Peng ZH. Up-regulation of microRNA-155 promotes cancer cell invasion and predicts poor survival of hepatocellular carcinoma following liver transplantation. J Cancer Res Clin Oncol 2012; 138: 153-161 [PMID: 22071603 DOI: 10.1007/s00432-011-1076-z]
53. Fornari F, Gramantieri L, Giovannini C, Veronese A, Ferra-cin M, Sabbioni S, Calin GA, Grazi GL, Croce CM, Tavolari S, Chieco P, Negrini M, Bolondi L. MiR-122/cyclin G1 interaction modulates p53 activity and affects doxorubicin sensitivity of human hepatocarcinoma cells. Cancer Res 2009; 69: 5761-5767 [PMID: 19584283 DOI: 10.1158/0008-5472. CAN-08-4797]
54. Fornari F, Milazzo M, Chieco P, Negrini M, Calin GA, Grazi GL, Pollutri D, Croce CM, Bolondi L, Gramantieri L. MiR-199a-3p regulates mTOR and c-Met to influence the doxorubicin sensitivity of human hepatocarcinoma cells. Cancer Res 2010; 70: 5184-5193 [PMID: 20501828 DOI: 10.1158/0008-5472.CAN-10-0145]
55. Yokoo H, Kondo T, Okano T, Nakanishi K, Sakamoto M, Kosuge T, Todo S, Hirohashi S. Protein expression associated with early intrahepatic recurrence of hepatocellular carcinoma after curative surgery. Cancer Sci 2007; 98: 665-673 [PMID: 17391314]
56. Yi X, Luk JM, Lee NP, Peng J, Leng X, Guan XY, Lau GK, Be-retta L, Fan ST. Association of mortalin (HSPA9) with liver cancer metastasis and prediction for early tumor recurrence. Mol Cell Proteomics 2008; 7: 315-325 [PMID: 17934217]
57. Cheng J, Xie HY, Xu X, Wu J, Wei X, Su R, Zhang W, Lv Z, Zheng S, Zhou L. NDRG1 as a biomarker for metastasis, recurrence and of poor prognosis in hepatocellular carcinoma. Cancer Lett 2011; 310: 35-45 [PMID: 21763068 DOI: 10.1016/ j.canlet.2011.06.001]
58. Bai DS, Dai Z, Zhou J, Liu YK, Qiu SJ, Tan CJ, Shi YH, Huang C, Wang Z, He YF, Fan J. Capn4 overexpression underlies tumor invasion and metastasis after liver transplantation for hepatocellular carcinoma. Hepatology 2009; 49: 460-470 [PMID: 19053044 DOI: 10.1002/hep.22638]
59. Orimo T, Ojima H, Hiraoka N, Saito S, Kosuge T, Kakisaka T, Yokoo H, Nakanishi K, Kamiyama T, Todo S, Hirohashi S, Kondo T. Proteomic profling reveals the prognostic value of adenomatous polyposis coli-end-binding protein 1 in hepa-tocellular carcinoma. Hepatology 2008; 48: 1851-1863 [PMID: 18937283 DOI: 10.1002/hep.22552]
60. Kanamori H, Kawakami T, Effendi K, Yamazaki K, Mori T, Ebinuma H, Masugi Y, Du W, Nagasaka K, Ogiwara A, Kyono Y, Tanabe M, Saito H, Hibi T, Sakamoto M. Identif-cation by differential tissue proteome analysis of talin-1 as a novel molecular marker of progression of hepatocellular carcinoma. Oncology 2011; 80: 406-415 [PMID: 21846996 DOI: 10.1159/000330734]
61. Beyoǧlu D, Idle JR. The metabolomic window into hepatobi-liary disease. J Hepatol 2013; 59: 842-858 [PMID: 23714158]
62. Soga T, Sugimoto M, Honma M, Mori M, Igarashi K, Ka-shikura K, Ikeda S, Hirayama A, Yamamoto T, Yoshida H, Otsuka M, Tsuji S, Yatomi Y, Sakuragawa T, Watanabe H, Nihei K, Saito T, Kawata S, Suzuki H, Tomita M, Suematsu M. Serum metabolomics reveals γ-glutamyl dipeptides as biomarkers for discrimination among different forms of liver disease. J Hepatol 2011; 55: 896-905 [PMID: 21334394 DOI: 10.1016/j.jhep.2011.01.031]
63. Nahon P, Amathieu R, Triba MN, Bouchemal N, Nault JC, Ziol M, Seror O, Dhonneur G, Trinchet JC, Beaugrand M, Le Moyec L. Identifcation of serum proton NMR metabolo-mic fingerprints associated with hepatocellular carcinoma in patients with alcoholic cirrhosis. Clin Cancer Res 2012; 18: 6714-6722 [PMID: 23136190 DOI: 10.1158/1078-0432. CCR-12-1099]
64. Wang B, Chen D, Chen Y, Hu Z, Cao M, Xie Q, Chen Y, Xu J, Zheng S, Li L. Metabonomic profles discriminate hepatocel-lular carcinoma from liver cirrhosis by ultraperformance liquid chromatography-mass spectrometry. J Proteome Res 2012; 11: 1217-1227 [PMID: 22200553 DOI: 10.1021/pr2009252]
65. Ressom HW, Xiao JF, Tuli L, Varghese RS, Zhou B, Tsai TH, Ranjbar MR, Zhao Y, Wang J, Di Poto C, Cheema AK, Tadesse MG, Goldman R, Shetty K. Utilization of metabo-lomics to identify serum biomarkers for hepatocellular carcinoma in patients with liver cirrhosis. Anal Chim Acta 2012; 743: 90-100 [PMID: 22882828 DOI: 10.1016/j.aca.2012.07.013]
66. Chen T, Xie G, Wang X, Fan J, Qiu Y, Zheng X, Qi X, Cao Y, Su M, Wang X, Xu LX, Yen Y, Liu P, Jia W. Serum and urine metabolite profiling reveals potential biomarkers of human hepatocellular carcinoma. Mol Cell Proteomics 2011; 10: M110.004945 [PMID: 21518826 DOI: 10.1074/mcp. M110.004945]
67. Tan Y, Yin P, Tang L, Xing W, Huang Q, Cao D, Zhao X, Wang W, Lu X, Xu Z, Wang H, Xu G. Metabolomics study of stepwise hepatocarcinogenesis from the model rats to patients: potential biomarkers effective for small hepatocellular carcinoma diagnosis. Mol Cell Proteomics 2012; 11: M111.010694 [PMID: 22084000 DOI: 10.1074/mcp. M111.010694]
68. Ye G, Zhu B, Yao Z, Yin P, Lu X, Kong H, Fan F, Jiao B, Xu G. Analysis of urinary metabolic signatures of early hepatocellular carcinoma recurrence after surgical removal using gas chromatography-mass spectrometry. J Proteome Res 2012; 11: 4361-4372 [PMID: 22768978 DOI: 10.1021/pr300502v]
69. Beyoǧlu D, Imbeaud S, Maurhofer O, Bioulac-Sage P, Zucman-Rossi J, Dufour JF, Idle JR. Tissue metabolomics of hepatocellular carcinoma: tumor energy metabolism and the role of transcriptomic classifcation. Hepatology 2013; 58: 229-238 [PMID: 23463346 DOI: 10.1002/hep.26350]