Immunohistochemistry-based prognostic biomarkers in NSCLC: Novel findings on the road to clinical use?

Expert Review of Molecular Diagnostics

Volumn 15, Issue 4, 2015, Pages 471-490

  Lindskog, Cecilia ^a,c   Edlund, Karolina ^b   Mattsson, Johanna Sofia Margareta ^c   Micke, Patrick ^c  

^a UPPSALA UNIVERSITY   (Sweden)

^b TU DORTMUND UNIVERSITY   (Germany)

^c UPPSALA UNIVERSITY   (Sweden)

Author keywords

biomarker; immunohistochemistry; lung cancer; patients; prognosis; protein

Indexed keywords

PROTEIN; TUMOR MARKER;

CANCER DIAGNOSIS; CANCER PROGNOSIS; CANCER SURVIVAL; DISEASE ASSOCIATION; HUMAN; IMMUNOHISTOCHEMISTRY; NON SMALL CELL LUNG CANCER; PROTEIN EXPRESSION; REVIEW; SAMPLE SIZE; CARCINOMA, NON-SMALL-CELL LUNG; LUNG NEOPLASMS; MORTALITY; PROCEDURES; PROGNOSIS; REPRODUCIBILITY; STANDARDS;

BIOMARKERS, TUMOR; CARCINOMA, NON-SMALL-CELL LUNG; HUMANS; IMMUNOHISTOCHEMISTRY; LUNG NEOPLASMS; PROGNOSIS; REPRODUCIBILITY OF RESULTS;

EID: 84925657466     PISSN: 14737159     EISSN: 17448352     Source Type: Journal    
DOI: 10.1586/14737159.2015.1002772     Document Type: Review

References (174)

1. Siegel R, Ma J, Zou Z, et al. Cancer statistics, 2014. CA Cancer J Clin 2014;64: 9-29
2. Rami-Porta R, Crowley JJ, Goldstraw P. The revised TNM staging system for lung cancer. Ann Thorac Cardiovasc Surg 2009;15:4-9
3. Weir BA, Woo MS, Getz G, et al. Characterizing the cancer genome in lung adenocarcinoma. Nature 2007;450:893-8
4. Imielinski M, Berger AH, Hammerman PS, et al. Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell 2012;150:1107-20
5. Cancer Genome Atlas Research Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature 2012;489:519-25
6. Reck M, Heigener DF, Mok T, et al. Management of non-small-cell lung cancer: recent developments. Lancet 2013;382: 709-19
7. Sculier JP, Chansky K, Crowley JJ, et al. The impact of additional prognostic factors on survival and their relationship with the anatomical extent of disease expressed by the 6th Edition of the TNM Classification of Malignant Tumors and the proposals for the 7th Edition. J Thorac Oncol 2008;3: 457-66
8. Micke P, Faldum A, Metz T, et al. Staging small cell lung cancer: Veterans Administration Lung Study Group versus International Association for the Study of Lung Cancer-what limits limited disease? Lung Cancer 2002;37:271-6
9. Travis WD. Pathology of lung cancer. Clin Chest Med 2011;32:669-92
10. Rusch VW, Rice TW, Crowley J, et al. The seventh edition of the American Joint Committee on Cancer/International Union Against Cancer Staging Manuals: the new era of data-driven revisions. J Thorac Cardiovasc Surg 2010;139:819-21
11. Gagnon B, Agulnik JS, Gioulbasanis I, et al. Montreal prognostic score: estimating survival of patients with non-small cell lung cancer using clinical biomarkers. Br J Cancer 2013;109:2066-71
12. Brzezianska E, Dutkowska A, Antczak A. The significance of epigenetic alterations in lung carcinogenesis. Mol Biol Rep 2013;40: 309-25
13. Director's Challenge Consortium for the Molecular Classification of Lung A. Shedden K, Taylor JM, et al. Gene expression-based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study. Nat Med 2008;14:822-7
14. Zhu CQ, Strumpf D, Li CY, et al. Prognostic gene expression signature for squamous cell carcinoma of lung. Clin Cancer Res 2010;16:5038-47
15. Van Laar RK. Genomic signatures for predicting survival and adjuvant chemotherapy benefit in patients with non-small-cell lung cancer. BMC Med Genomics 2012;5:30
16. Subramanian J, Simon R. Gene expression-based prognostic signatures in lung cancer: ready for clinical use? J Natl Cancer Inst 2010;102:464-74
17. Suzuki K, Kachala SS, Kadota K, et al. Prognostic immune markers in non-small cell lung cancer. Clin Cancer Res 2011;17: 5247-56
18. Paulsson J, Micke P. Prognostic relevance of cancer-associated fibroblasts in human cancer. Semin Cancer Biol 2014;25:61-8
19. Zhu CQ, Shih W, Ling CH, et al. Immunohistochemical markers of prognosis in non-small cell lung cancer: a review and proposal for a multiphase approach to marker evaluation. J Clin Pathol 2006;59: 790-800
20. Jakobsen JN, Sorensen JB. Clinical impact of ki-67 labeling index in non-small cell lung cancer. Lung Cancer 2013;79:1-7
21. Paci M, Rapicetta C, Maramotti S. New biomarkers for lung cancer. Expert Opin Med Diagn 2010;4:201-24
22. Pestell RG. New roles of cyclin D1. Am J Pathol 2013;183:3-9
23. Nishio M, Koshikawa T, Yatabe Y, et al. Prognostic significance of cyclin D1 and retinoblastoma expression in combination with p53 abnormalities in primary, resected non-small cell lung cancers. Clin Cancer Res 1997;3:1051-8
24. Zhang LQ, Jiang F, Xu L, et al. The role of cyclin D1 expression and patient's survival in non-small-cell lung cancer: a systematic review with meta-analysis. Clin Lung Cancer 2012;13:188-95
25. Berghmans T, Meert AP, Martin B, et al. Prognostic role of epidermal growth factor receptor in stage III nonsmall cell lung cancer. Eur Respir J 2005;25:329-35
26. Meert AP, Martin B, Delmotte P, et al. The role of EGF-R expression on patient survival in lung cancer: a systematic review with meta-analysis. Eur Respir J 2002;20: 975-81
27. Steels E, Paesmans M, Berghmans T, et al. Role of p53 as a prognostic factor for survival in lung cancer: a systematic review of the literature with a meta-analysis. Eur Respir J 2001;18:705-19
28. Barlesi F, Pinot D, Legoffic A, et al. Positive thyroid transcription factor 1 staining strongly correlates with survival of patients with adenocarcinoma of the lung. Br J Cancer 2005;93:450-2
29. Hammond ME. ASCO-CAP guidelines for breast predictive factor testing: an update. Appl Immunohistochem Mol Morphol 2011;19:499-500
30. Martin B, Paesmans M, Mascaux C, et al. Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis. Br J Cancer 2004;91:2018-25
31. Available from: www.proteinatlas.org
32. Polanski M, Anderson NL. A list of candidate cancer biomarkers for targeted proteomics. Biomark Insights 2007;1:1-48
33. Forbes SA, Bindal N, Bamford S, et al. COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer. Nucleic Acids Res 2011;39: D945-50
34. Tamborero D, Gonzalez-Perez A, Perez-Llamas C, et al. Comprehensive identification of mutational cancer driver genes across 12 tumor types. Sci Rep 2013;3:2650
35. Lawrence MS, Stojanov P, Mermel CH, et al. Discovery and saturation analysis of cancer genes across 21 tumour types. Nature 2014;505:495-501
36. Suzuki K, Kadota K, Sima CS, et al. Clinical impact of immune microenvironment in stage I lung adenocarcinoma: tumor interleukin-12 receptor beta2 (IL-12Rbeta2), IL-7R, and stromal FoxP3/CD3 ratio are independent predictors of recurrence. J Clin Oncol 2013;31:490-8
37. Liu ZG, Lei YY, Li WW, et al. The co-expression of ERbeta2 and IL-12Rbeta2 is better prognostic factor in non-small-cell lung cancer progression. Med Oncol 2013;30:592
38. Ming J, Zhang Q, Qiu X, et al. Interleukin 7/interleukin 7 receptor induce c-Fos/c-Jun-dependent vascular endothelial growth factor-D up-regulation: a mechanism of lymphangiogenesis in lung cancer. Eur J Cancer 2009;45:866-73
39. Davies M. New modalities of cancer treatment for NSCLC: focus on immunotherapy. Cancer Manag Res 2014;6: 63-75
40. Dieu-Nosjean MC, Antoine M, Danel C, et al. Long-term survival for patients with non-small-cell lung cancer with intratumoral lymphoid structures. J Clin Oncol 2008;26: 4410-17
41. Wakabayashi O, Yamazaki K, Oizumi S, et al. CD4+ T cells in cancer stroma, not CD8+ T cells in cancer cell nests, are associated with favorable prognosis in human non-small cell lung cancers. Cancer Sci 2003;94:1003-9
42. Welsh TJ, Green RH, Richardson D, et al. Macrophage and mast-cell invasion of tumor cell islets confers a marked survival advantage in non-small-cell lung cancer. J Clin Oncol 2005;23:8959-67
43. Petersen RP, Campa MJ, Sperlazza J, et al. Tumor infiltrating Foxp3+ regulatory T-cells are associated with recurrence in pathologic stage I NSCLC patients. Cancer 2006;107:2866-72
44. Ohtaki Y, Ishii G, Nagai K, et al. Stromal macrophage expressing CD204 is associated with tumor aggressiveness in lung adenocarcinoma. J Thorac Oncol 2010;5: 1507-15
45. Nakashima T, Liu D, Nakano J, et al. Wnt1 overexpression associated with tumor proliferation and a poor prognosis in non-small cell lung cancer patients. Oncol Rep 2008;19:203-9
46. Huang CL, Liu D, Ishikawa S, et al. Wnt1 overexpression promotes tumour progression in non-small cell lung cancer. Eur J Cancer 2008;44:2680-8
47. Xu X, Sun PL, Li JZ, et al. Aberrant Wnt1/beta-catenin expression is an independent poor prognostic marker of non-small cell lung cancer after surgery. J Thorac Oncol 2011;6:716-24
48. Li X, Wan L, Geng J, et al. Aldehyde dehydrogenase 1A1 possesses stem-like properties and predicts lung cancer patient outcome. J Thorac Oncol 2012;7:1235-45
49. Alamgeer M, Ganju V, Szczepny A, et al. The prognostic significance of aldehyde dehydrogenase 1A1 (ALDH1A1) and CD133 expression in early stage non-small cell lung cancer. Thorax 2013;68:1095-104
50. Jiang F, Qiu Q, Khanna A, et al. Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer. Mol Cancer Res 2009;7:330-8
51. Sullivan JP, Spinola M, Dodge M, et al. Aldehyde dehydrogenase activity selects for lung adenocarcinoma stem cells dependent on notch signaling. Cancer Res 2010;70: 9937-48
52. Shimada Y, Saji H, Nomura M, et al. Cancer stem cell-related marker expression in lung adenocarcinoma and relevance of histologic subtypes based on IASLC/ATS/ERS classification. Onco Targets Ther 2013;6:1597-604
53. Raz G, Allen KE, Kingsley C, et al. Hedgehog signaling pathway molecules and ALDH1A1 expression in early-stage non-small cell lung cancer. Lung Cancer 2012;76:191-6
54. Janikova M, Skarda J, Dziechciarkova M, et al. Identification of CD133+/nestin+ putative cancer stem cells in non-small cell lung cancer. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2010;154: 321-6
55. Ryuge S, Sato Y, Wang GQ, et al. Prognostic significance of nestin expression in resected non-small cell lung cancer. Chest 2011;139:862-9
56. Ryuge S, Sato Y, Jiang SX, et al. Prognostic impact of nestin expression in resected large cell neuroendocrine carcinoma of the lung. Lung Cancer 2012;77:415-20
57. Sterlacci W, Savic S, Fiegl M, et al. Putative stem cell markers in non-small-cell lung cancer: a clinicopathologic characterization. J Thorac Oncol 2014;9:41-9
58. Marcato P, Dean CA, Giacomantonio CA, et al. Aldehyde dehydrogenase: its role as a cancer stem cell marker comes down to the specific isoform. Cell Cycle 2011;10: 1378-84
59. Lendahl U, Zimmerman LB, McKay RD. CNS stem cells express a new class of intermediate filament protein. Cell 1990;60: 585-95
60. O'Connor ML, Xiang D, Shigdar S, et al. Cancer stem cells: a contentious hypothesis now moving forward. Cancer Lett 2014;344:180-7
61. O'Shannessy DJ, Yu G, Smale R, et al. Folate receptor alpha expression in lung cancer: diagnostic and prognostic significance. Oncotarget 2012;3:414-25
62. Christoph DC, Asuncion BR, Hassan B, et al. Significance of folate receptor alpha and thymidylate synthase protein expression in patients with non-small-cell lung cancer treated with pemetrexed. J Thorac Oncol 2013;8:19-30
63. Gronberg BH, Lund-Iversen M, Strom EH, et al. Associations between TS. TTF-1, FR-alpha, FPGS, and overall survival in patients with advanced non-small-cell lung cancer receiving pemetrexed plus carboplatin or gemcitabine plus carboplatin as first-line chemotherapy. J Thorac Oncol 2013;8: 1255-64
64. Wang H, Wang W, Wang X, et al. Reduced N-Myc downstream-regulated gene 2 expression is associated with CD24 upregulation and poor prognosis in patients with lung adenocarcinoma. Med Oncol 2012;29:3162-8
65. Li SJ, Wang WY, Li B, et al. Expression of NDRG2 in human lung cancer and its correlation with prognosis. Med Oncol 2013;30:421
66. Azuma K, Kawahara A, Hattori S, et al. NDRG1/Cap43/Drg-1 may predict tumor angiogenesis and poor outcome in patients with lung cancer. J Thorac Oncol 2012;7: 779-89
67. Chen CD, Wang CS, Huang YH, et al. Overexpression of CLIC1 in human gastric carcinoma and its clinicopathological significance. Proteomics 2007;7:155-67
68. Zhang Y, Zhang S, Wang X, et al. Prognostic significance of FOXP1 as an oncogene in hepatocellular carcinoma. J Clin Pathol 2012;65:528-33
69. Yamada S, Sato F, Xia H, et al. Forkhead box P1 overexpression and its clinicopathologic significance in peripheral T-cell lymphoma, not otherwise specified. Hum Pathol 2012;43:1322-7
70. Barrans SL, Fenton JA, Banham A, et al. Strong expression of FOXP1 identifies a distinct subset of diffuse large B-cell lymphoma (DLBCL) patients with poor outcome. Blood 2004;104:2933-5
71. Yang Q, Luo GY, Li Y, et al. Expression of Rac-1 related to tumor depth, lymph node metastasis and patient prognosis in esophageal squamous cell carcinoma. Med Oncol 2013;30:689
72. Kamai T, Shirataki H, Nakanishi K, et al. Increased Rac1 activity and Pak1 overexpression are associated with lymphovascular invasion and lymph node metastasis of upper urinary tract cancer. BMC Cancer 2010;10:164
73. Huang Y, Liu D, Chen B, et al. Loss of Bad expression confers poor prognosis in non-small cell lung cancer. Med Oncol 2012;29:1648-55
74. Chen HH, Yan JJ, Chen WC, et al. Predictive and prognostic value of human copper transporter 1 (hCtr1) in patients with stage III non-small-cell lung cancer receiving first-line platinum-based doublet chemotherapy. Lung Cancer 2012;75: 228-34
75. Takeuchi K, Ogata S, Nakanishi K, et al. LAT1 expression in non-small-cell lung carcinomas: analyses by semiquantitative reverse transcription-PCR (237 cases) and immunohistochemistry (295 cases). Lung Cancer 2010;68:58-65
76. Kaira K, Oriuchi N, Imai H, et al. Prognostic significance of L-type amino acid transporter 1 expression in resectable stage I-III nonsmall cell lung cancer. Br J Cancer 2008;98:742-8
77. Kaira K, Oriuchi N, Imai H, et al. Prognostic significance of L-type amino acid transporter 1 (LAT1) and 4F2 heavy chain (CD98) expression in stage I pulmonary adenocarcinoma. Lung Cancer 2009;66: 120-6
78. Kaira K, Oriuchi N, Imai H, et al. L-type amino acid transporter 1 (LAT1) is frequently expressed in thymic carcinomas but is absent in thymomas. J Surg Oncol 2009;99:433-8
79. Kaira K, Oriuchi N, Imai H, et al. Prognostic significance of L-type amino acid transporter 1 (LAT1) and 4F2 heavy chain (CD98) expression in early stage squamous cell carcinoma of the lung. Cancer Sci 2009;100:248-54
80. Imai H, Kaira K, Oriuchi N, et al. L-type amino acid transporter 1 expression is a prognostic marker in patients with surgically resected stage I non-small cell lung cancer. Histopathology 2009;54:804-13
81. Imai H, Kaira K, Oriuchi N, et al. Inhibition of L-type amino acid transporter 1 has antitumor activity in non-small cell lung cancer. Anticancer Res 2010;30: 4819-28
82. Kaira K, Oriuchi N, Imai H, et al. Prognostic significance of L-type amino acid transporter 1 (LAT1) and 4F2 heavy chain (CD98) expression in surgically resectable stage III non-small cell lung cancer. Exp Ther Med 2010;1:799-808
83. Kaira K, Oriuchi N, Imai H, et al. CD98 expression is associated with poor prognosis in resected non-small-cell lung cancer with lymph node metastases. Ann Surg Oncol 2009;16:3473-81
84. Chiang YY, Chen SL, Hsiao YT, et al. Nuclear expression of dynamin-related protein 1 in lung adenocarcinomas. Mod Pathol 2009;22:1139-50
85. Kato T, Daigo Y, Aragaki M, et al. Overexpression of KIAA0101 predicts poor prognosis in primary lung cancer patients. Lung Cancer 2012;75:110-18
86. Schleich S, Strassburger K, Janiesch PC, et al. DENR-MCT-1 promotes translation re-initiation downstream of uORFs to control tissue growth. Nature 2014;512: 208-12
87. Povlsen LK, Beli P, Wagner SA, et al. Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass. Nat Cell Biol 2012;14:1089-98
88. Gold KA, Kim ES, Liu DD, et al. Prediction of survival in resected non-small cell lung cancer using a protein expression-based risk model: implications for personalized chemoprevention and therapy. Clin Cancer Res 2014;20:1946-54
89. McShane LM, Altman DG, Sauerbrei W, et al. Reporting recommendations for tumor MARKer prognostic studies (REMARK). Nat Clin Pract Urol 2005;2:416-22
90. Howat WJ, Lewis A, Jones P, et al. Antibody validation of immunohistochemistry for biomarker discovery: recommendations of a consortium of academic and pharmaceutical based histopathology researchers. Methods 2014; 70(1):34-8
91. O'Hurley G, Sjostedt E, Rahman A, et al. Garbage in, garbage out: a critical evaluation of strategies used for validation of immunohistochemical biomarkers. Mol Oncol 2014;8:783-98
92. Saper CB. An open letter to our readers on the use of antibodies. J Comp Neurol 2005;493:477-8
93. Gore AC. Editorial: antibody validation requirements for articles published in endocrinology. Endocrinology 2013;154: 579-80
94. Barrett T, Wilhite SE, Ledoux P, et al. NCBI GEO: archive for functional genomics data sets-update. Nucleic Acids Res 2013;41:D991-5
95. Rustici G, Kolesnikov N, Brandizi M, et al. ArrayExpress update-trends in database growth and links to data analysis tools. Nucleic Acids Res 2013;41:D987-90
96. Bjorling E, Uhlen M. Antibodypedia, a portal for sharing antibody and antigen validation data. Mol Cell Proteomics 2008;7:2028-37
97. Fiore C, Bailey D, Conlon N, et al. Utility of multispectral imaging in automated quantitative scoring of immunohistochemistry. J Clin Pathol 2012;65:496-502
98. Kay EW, Walsh CJ, Cassidy M, et al. C-erbB-2 immunostaining: problems with interpretation. J Clin Pathol 1994;47: 816-22
99. Conway C, Dobson L, O'Grady A, et al. Virtual microscopy as an enabler of automated/quantitative assessment of protein expression in TMAs. Histochem Cell Biol 2008;130:447-63
100. Taylor CR, Levenson RM. Quantification of immunohistochemistry-issues concerning methods, utility and semiquantitative assessment II. Histopathology 2006;49: 411-24
101. Biaoxue R, Xiling J, Shuanying Y, et al. Upregulation of Hsp90-beta and annexin A1 correlates with poor survival and lymphatic metastasis in lung cancer patients. J Exp Clin Cancer Res 2012;31:70
102. Tikhmyanova N, Little JL, Golemis EA. CAS proteins in normal and pathological cell growth control. Cell Mol Life Sci 2010; 67(7):1025-48
103. Barrett A, Pellet-Many C, Zachary IC, et al. p130Cas: a key signalling node in health and disease. Cell Signal 2013;25(4):766-77
104. Miao Y, Li AL, Wang L, et al. Expression of p130cas, E-cadherin and b-catenin and their correlation with clinicopathological parameters in non-small cell lung cancer: p130cas over-expression predicts poor prognosis. Folia Histochem Cytobiol 2012; 50(3):392-7
105. Deng B, Huang W, Tan QY, et al. Breast cancer anti-estrogen resistance protein 1 (BCAR1/p130cas) in pulmonary disease tissue and serum. Mol Diagn Ther 2011; 15(1):31-40
106. Coyne CB, Gambling TM, Boucher RC, et al. Role of claudin interactions in airway tight junctional permeability. Am J Physiol Lung Cell Mol Physiol 2003;285(5): L1166-78
107. Micke P, Mattsson JS, Edlund K, et al. Aberrantly activated claudin 6 and 18.2 as potential therapy targets in non-small-cell lung cancer. Int J Cancer 2014;135(9): 2206-14
108. Soini Y. Claudins in lung diseases. Respir Res 2011;12:70
109. Chao YC, Pan SH, Yang SC, et al. Claudin-1 is a metastasis suppressor and correlates with clinical outcome in lung adenocarcinoma. Am J Respir Crit Care Med 2009;179(2):123-33
110. Zhang Z, Wang A, Sun B, et al. Expression of CLDN1 and CLDN10 in lung adenocarcinoma in situ and invasive lepidic predominant adenocarcinoma. J Cardiothorac Surg 2013;8:95
111. Silvera D, Formenti SC, Schneider RJ. Translational control in cancer. Nat Rev Cancer 2010;10(4):254-66
112. Wendel HG, Silva RL, Malina A, et al. Dissecting eIF4E action in tumorigenesis. Genes Dev 2007;21(24):3232-7
113. Yoshizawa A, Fukuoka J, Shimizu S, et al. Overexpression of phospho-eIF4E is associated with survival through AKT pathway in non-small cell lung cancer. Clin Cancer Res 2010;16(1):240-8
114. Seki N, Takasu T, Sawada S, et al. Prognostic significance of expression of eukaryotic initiation factor 4E and 4E binding protein 1 in patients with pathological stage I invasive lung adenocarcinoma. Lung Cancer 2010;70(3): 329-34
115. Wang R, Geng J, Wang JH, et al. Overexpression of eukaryotic initiation factor 4E (eIF4E) and its clinical significance in lung adenocarcinoma. Lung Cancer 2009;66(2):237-44
116. Khoury T, Alrawi S, Ramnath N, et al. Eukaryotic initiation factor-4E and cyclin D1 expression associated with patient survival in lung cancer. Clin Lung Cancer 2009;10(1):58-66
117. Yang YA, Yu J. EZH2, an epigenetic driver of prostate cancer. Protein Cell 2013;4(5): 331-41
118. Takawa M, Masuda K, Kunizaki M, et al. Validation of the histone methyltransferase EZH2 as a therapeutic target for various types of human cancer and as a prognostic marker.Cancer Sci. 2011;102(7):1298-305
119. Behrens C, Solis LM, Lin H, et al. EZH2 protein expression associates with the early pathogenesis, tumor progression, and prognosis of non-small cell lung carcinoma. Clin Cancer Res 2013;19(23):6556-65
120. Kikuchi J, Kinoshita I, Shimizu Y, et al. Distinctive expression of the polycomb group proteins Bmi1 polycomb ring finger oncogene and enhancer of zeste homolog 2 in nonsmall cell lung cancers and their clinical and clinicopathologic significance. Cancer 2010;116(12):3015-24
121. Huqun, Ishikawa R, Zhang J, et al. Enhancer of zeste homolog 2 is a novel prognostic biomarker in nonsmall cell lung cancer. Cancer 2012;118(6):1599-606
122. Thomas A, Maltzman J, Hassan R. Farletuzumab in lung cancer. Lung Cancer 2013;80(1):15-18
123. Halasi M, Gartel AL. FOX(M1) news-it is cancer. Mol Cancer Ther 2013;12(3): 245-54
124. Yang DK, Son CH, Lee SK, et al. Forkhead box M1 expression in pulmonary squamous cell carcinoma: correlation with clinicopathologic features and its prognostic significance. Hum Pathol 2009;40(4): 464-70
125. Xu N, Wu SD, Wang H, et al. Involvement of FoxM1 in non-small cell lung cancer recurrence. Asian Pac J Cancer Prev 2012;13(9):4739-43
126. Xu N, Jia D, Chen W, et al. FoxM1 is associated with poor prognosis of non-small cell lung cancer patients through promoting tumor metastasis. PLoS One 2013;8(3): e59412
127. Khanna A, Pimanda JE, Westermarck J. Cancerous inhibitor of protein phosphatase 2A, an emerging human oncoprotein and a potential cancer therapy target. Cancer Res 2013;73(22):6548-53
128. Côme C, Laine A, Chanrion M, et al. CIP2A is associated with human breast cancer aggressivity. Clin Cancer Res 2009; 15(16):5092-100
129. Fang Y, Li Z, Wang X, Zhang S. CIP2A is overexpressed in human ovarian cancer and regulates cell proliferation and apoptosis. Tumour Biol 2012;33(6):2299-306
130. Dong QZ, Wang Y, Dong XJ, et al. CIP2A is overexpressed in non-small cell lung cancer and correlates with poor prognosis. Ann Surg Oncol 2011;18(3): 857-65
131. Xu P, Xu XL, Huang Q, et al. CIP2A with survivin protein expressions in human non-small-cell lung cancer correlates with prognosis. Med Oncol 2012;29(3):1643-7
132. Pan SH, Chao YC, Hung PF, et al. The ability of LCRMP-1 to promote cancer invasion by enhancing filopodia formation is antagonized by CRMP-1. J Clin Invest 2011;121(8):3189-205
133. Pan SH, Chao YC, Chen HY, et al. Long form collapsin response mediator protein-1 (LCRMP-1) expression is associated with clinical outcome and lymph node metastasis in non-small cell lung cancer patients. Lung Cancer 2010;67(1):93-100
134. Semenza GL. Cancer-stromal cell interactions mediated by hypoxia-inducible factors promote angiogenesis, lymphangiogenesis, and metastasis. Oncogene 2013;32(35):4057-63
135. Wilgus ML, Borczuk AC, Stoopler M, et al. Lysyl oxidase: a lung adenocarcinoma biomarker of invasion and survival. Cancer 2011;117(10):2186-91
136. Ping W, Jiang WY, Chen WS, et al. Expression and significance of hypoxia inducible factor-1a and lysyl oxidase in non-small cell lung cancer. Asian Pac J Cancer Prev 2013;14(6):3613-18
137. Kearsey SE, Labib K. MCM proteins: evolution, properties, and role in DNA replication. Biochim Biophys Acta 1998;1398(2):113-36
138. Toyokawa G, Masuda K, Daigo Y, et al. Minichromosome Maintenance Protein 7 is a potential therapeutic target in human cancer and a novel prognostic marker of non-small cell lung cancer. Mol Cancer 2011;10:65
139. Haruki T, Shomori K, Hamamoto Y, et al. Geminin expression in small lung adenocarcinomas: implication of prognostic significance. Lung Cancer 2011;71(3): 356-62
140. Fujioka S, Shomori K, Nishihara K, et al. Expression of minichromosome maintenance 7 (MCM7) in small lung adenocarcinomas (pT1): prognostic implication. Lung Cancer 2009;65(2):223-9
141. Toh Y, Nicolson GL. The role of the MTA family and their encoded proteins in human cancers: molecular functions and clinical implications. Clin Exp Metastasis 2009;26(3):215-27
142. Yu Y, Wang Z, Zhang MY, et al. Relation between prognosis and expression of metastasis-associated protein 1 in stage I non-small cell lung cancer. Interact Cardiovasc Thorac Surg 2011;12(2):166-9
143. Li SH, Tian H, Yue WM, et al. Overexpression of metastasis-associated protein 1 is significantly correlated with tumor angiogenesis and poor survival in patients with early-stage non-small cell lung cancer. Ann Surg Oncol 2011;18(7): 2048-56
144. Emdad L, Sarkar D, Su ZZ, et al. Astrocyte elevated gene-1: recent insights into a novel gene involved in tumor progression, metastasis and neurodegeneration. Pharmacol Ther 2007;114(2):155-70
145. Sun S, Ke Z, Wang F, et al. Overexpression of astrocyte-elevated gene-1 is closely correlated with poor prognosis in human non-small cell lung cancer and mediates its metastasis through up-regulation of matrix metalloproteinase-9 expression. Hum Pathol 2012;43(7):1051-60
146. Ke ZF, Mao X, Zeng C, et al. AEG-1 expression characteristics in human non-small cell lung cancer and its relationship with apoptosis. Med Oncol 2013;30(1):383
147. Song L, Li W, Zhang H, et al. Over-expression of AEG-1 significantly associates with tumour aggressiveness and poor prognosis in human non-small cell lung cancer. J Pathol 2009;219(3):317-26
148. Tien JC, Xu J. Steroid receptor coactivator-3 as a potential molecular target for cancer therapy. Expert Opin Ther Targets 2012;16(11):1085-96
149. He LR, Zhao HY, Li BK, et al. Overexpression of AIB1 negatively affects survival of surgically resected non-small-cell lung cancer patients. Ann Oncol 2010; 21(8):1675-81
150. Cai D, Shames DS, Raso MG, et al. Steroid receptor coactivator-3 expression in lung cancer and its role in the regulation of cancer cell survival and proliferation. Cancer Res 2010;70(16):6477-85
151. Melotte V, Qu X, Ongenaert M, et al. The N-myc downstream regulated gene (NDRG) family: diverse functions, multiple applications. FASEB J 2010;24(11):4153-66
152. Yao L, Zhang J, Liu X. NDRG2: a Myc-repressed gene involved in cancer and cell stress. Acta Biochim Biophys Sin (Shanghai) 2008;40(7):625-35
153. Kondo S, Iwata S, Yamada T, et al. Impact of the integrin signaling adaptor protein NEDD9 on prognosis and metastatic behavior of human lung cancer. Clin Cancer Res 2012;18(22):6326-38
154. Miao Y, Li AL, Wang L, et al. Overexpression of NEDD9 is associated with altered expression of E-Cadherin, b-Catenin and N-Cadherin and predictive of poor prognosis in non-small cell lung cancer. Pathol Oncol Res 2013;19(2):281-6
155. Park JH, Nishidate T, Nakamura Y, Katagiri T. Critical roles of T-LAK cell-originated protein kinase in cytokinesis. Cancer Sci 2010;101(2):403-11
156. Simons-Evelyn M, Bailey-Dell K, Toretsky JA, et al. PBK/TOPK is a novel mitotic kinase which is upregulated in Burkitt's lymphoma and other highly proliferative malignant cells. Blood Cells Mol Dis 2001;27(5):825-9
157. Shih MC, Chen JY, Wu YC, et al. TOPK/PBK promotes cell migration via modulation of the PI3K/PTEN/AKT pathway and is associated with poor prognosis in lung cancer. Oncogene 2012; 31(19):2389-400
158. Lei B, Liu S, Qi W, et al. PBK/TOPK expression in non-small-cell lung cancer: its correlation and prognostic significance with Ki67 and p53 expression. Histopathology 2013;63(5):696-703
159. Wei DC, Yeh YC, Hung JJ, et al. Overexpression of T-LAK cell-originated protein kinase predicts poor prognosis in patients with stage I lung adenocarcinoma. Cancer Sci 2012;103(4):731-8
160. Lu X, Nguyen TA, Moon SH, et al. The type 2C phosphatase Wip1: an oncogenic regulator of tumor suppressor and DNA damage response pathways. Cancer Metastasis Rev 2008;27(2):123-35
161. Li J, Yang Y, Peng Y, et al. Oncogenic properties of PPM1D located within a breast cancer amplification epicenter at 17q23. Nat Genet 2002;31(2):133-4
162. Bulavin DV, Demidov ON, Saito S, et al. Amplification of PPM1D in human tumors abrogates p53 tumor-suppressor activity. Nat Genet 2002;31(2):210-15
163. Loukopoulos P, Shibata T, Katoh H, et al. Genome-wide array-based comparative genomic hybridization analysis of pancreatic adenocarcinoma: identification of genetic indicators that predict patient outcome. Cancer Sci 2007;98(3):392-400
164. Satoh N, Maniwa Y, Bermudez VP, et al. Oncogenic phosphatase Wip1 is a novel prognostic marker for lung adenocarcinoma patient survival. Cancer Sci 2011;102(5): 1101-6
165. Fu Z, Sun G, Gu T. Proto-oncogene Wip1, a member of a new family of proliferative genes in NSCLC and its clinical significance. Tumour Biol 2014;35(4): 2975-81
166. Yuan H, Su L, Chen WY. The emerging and diverse roles of sirtuins in cancer: a clinical perspective. Onco Targets Ther 2013;6:1399-416
167. Noh SJ, Baek HA, Park HS, et al. Expression of SIRT1 and cortactin is associated with progression of non-small cell lung cancer. Pathol Res Pract 2013;209(6): 365-70
168. Zhang T, Rong N, Chen J, et al. SIRT1 expression is associated with the chemotherapy response and prognosis of patients with advanced NSCLC. PLoS One 2013;8(11):e79162
169. Nakanishi T, Tamai I. Solute carrier transporters as targets for drug delivery and pharmacological intervention for chemotherapy. J Pharm Sci 2011;100(9): 3731-50
170. Komatsu M, Kageyama S, Ichimura Y. p62/SQSTM1/A170: physiology and pathology. Pharmacol Res 2012;66(6):457-62
171. Inoue D, Suzuki T, Mitsuishi Y, et al. Accumulation of p62/SQSTM1 is associated with poor prognosis in patients with lung adenocarcinoma. Cancer Sci 2012;103(4): 760-6
172. Wang BS, Liu YZ, Yang Y, et al. Autophagy negatively regulates cancer cell proliferation via selectively targeting VPRBP. Clin Sci (Lond) 2013;124(3): 203-14
173. Anastas JN, Moon RT. WNT signalling pathways as therapeutic targets in cancer. Nat Rev Cancer 2013;13(1):11-26
174. Stewart DJ. Wnt signaling pathway in non-small cell lung cancer. J Natl Cancer Inst 2014;106(1):djt356