全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...
Microarrays  2013 

Lung Cancer Gene Signatures and Clinical Perspectives

DOI: 10.3390/microarrays2040318

Keywords: lung cancer, NSCLC, biomarker, gene signature, testing

Full-Text   Cite this paper   Add to My Lib

Abstract:

Microarrays have been used for more than two decades in preclinical research. The tumor transcriptional profiles were analyzed to select cancer-associated genes for in-deep functional characterization, to stratify tumor subgroups according to the histopathology or diverse clinical courses, and to assess biological and cellular functions behind these gene sets. In lung cancer—the main type of cancer causing mortality worldwide—biomarker research focuses on different objectives: the early diagnosis of curable tumor diseases, the stratification of patients with prognostic unfavorable operable tumors to assess the need for further therapy regimens, or the selection of patients for the most efficient therapies at early and late stages. In non-small cell lung cancer, gene and miRNA signatures are valuable to differentiate between the two main subtypes’ squamous and non-squamous tumors, a discrimination which has further implications for therapeutic schemes. Further subclassification within adenocarcinoma and squamous cell carcinoma has been done to correlate histopathological phenotype with disease outcome. Those tumor subgroups were assigned by diverse transcriptional patterns including potential biomarkers and therapy targets for future diagnostic and clinical applications. In lung cancer, none of these signatures have entered clinical routine for testing so far. In this review, the status quo of lung cancer gene signatures in preclinical and clinical research will be presented in the context of future clinical perspectives.

References

[1]  Alberg, A.J.; Brock, M.V.; Ford, J.G.; Samet, J.M.; Spivack, S.D. Epidemiology of lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013, 143, e1S–e29S, doi:10.1378/chest.12-2345.
[2]  Siegel, R.; Naishadham, D.; Jemal, A. Cancer statistics, 2013. Cancer J. Clin. 2013, 63, 11–30, doi:10.3322/caac.21166.
[3]  Subramanian, J.; Regenbogen, T.; Nagaraj, G.; Lane, A.; Devarakonda, S.; Zhou, G.; Govindan, R. Review of ongoing clinical trials in non-small-cell lung cancer: A status report for 2012 from the ClinicalTrials.gov Web site. J. Thoracic Oncol. 2013, 8, 860–865, doi:10.1097/JTO.0b013e318287c562.
[4]  Kovalchik, S.A.; Tammemagi, M.; Berg, C.D.; Caporaso, N.E.; Riley, T.L.; Korch, M.; Silvestri, G.A.; Chaturvedi, A.K.; Katki, H.A. Targeting of low-dose CT screening according to the risk of lung-cancer death. N. Engl. J. Med. 2013, 369, 245–254, doi:10.1056/NEJMoa1301851.
[5]  Aberle, D.R.; Abtin, F.; Brown, K. Computed tomography screening for lung cancer: Has it finally arrived? Implications of the national lung screening trial. J. Clin. Oncol. 2013, 31, 1002–1008, doi:10.1200/JCO.2012.43.3110.
[6]  Hassanein, M.; Callison, J.C.; Callaway-Lane, C.; Aldrich, M.C.; Grogan, E.L.; Massion, P.P. The state of molecular biomarkers for the early detection of lung cancer. Cancer Prev. Res. 2012, 5, 992–1006, doi:10.1158/1940-6207.CAPR-11-0441.
[7]  Chapman, C.J.; Healey, G.F.; Murray, A.; Boyle, P.; Robertson, C.; Peek, L.J.; Allen, J.; Thorpe, A.J.; Hamilton-Fairley, G.; Parsy-Kowalska, C.B.; et al. EarlyCDT?-Lung test: Improved clinical utility through additional autoantibody assays. Tumour Biol. 2012, 33, 1319–1326, doi:10.1007/s13277-012-0379-2.
[8]  Lam, S.; Boyle, P.; Healey, G.F.; Maddison, P.; Peek, L.; Murray, A.; Chapman, C.J.; Allen, J.; Wood, W.C.; Sewell, H.F.; et al. EarlyCDT-Lung: An immunobiomarker test as an aid to early detection of lung cancer. Cancer Prev. Res. 2011, 4, 1126–1134, doi:10.1158/1940-6207.CAPR-10-0328.
[9]  Macdonald, I.K.; Murray, A.; Healey, G.F.; Parsy-Kowalska, C.B.; Allen, J.; McElveen, J.; Robertson, C.; Sewell, H.F.; Chapman, C.J.; Robertson, J.F. Application of a high throughput method of biomarker discovery to improvement of the EarlyCDT?-Lung test. PLoS One 2012, 7, doi:10.1371/journal.pone.0051002.
[10]  Dietrich, D.; Kneip, C.; Raji, O.; Liloglou, T.; Seegebarth, A.; Schlegel, T.; Flemming, N.; Rausch, S.; Distler, J.; Fleischhacker, M.; et al. Performance evaluation of the DNA methylation biomarker SHOX2 for the aid in diagnosis of lung cancer based on the analysis of bronchial aspirates. Int. J. Oncol. 2012, 40, 825–832.
[11]  Darwiche, K.; Zarogoulidis, P.; Baehner, K.; Welter, S.; Tetzner, R.; Wohlschlaeger, J.; Theegarten, D.; Nakajima, T.; Freitag, L. Assessment of SHOX2 methylation in EBUS-TBNA specimen improves accuracy in lung cancer staging. Ann. Oncol. 2013, 24, 2866–2870, doi:10.1093/annonc/mdt365.
[12]  Nikolaidis, G.; Raji, O.Y.; Markopoulou, S.; Gosney, J.R.; Bryan, J.; Warburton, C.; Walshaw, M.; Sheard, J.; Field, J.K.; Liloglou, T. DNA methylation biomarkers offer improved diagnostic efficiency in lung cancer. Cancer Res. 2012, 72, 5692–5701, doi:10.1158/0008-5472.CAN-12-2309.
[13]  Bianchi, F.; Nicassio, F.; Marzi, M.; Belloni, E.; Dall’olio, V.; Bernard, L.; Pelosi, G.; Maisonneuve, P.; Veronesi, G.; di Fiore, P.P. A serum circulating miRNA diagnostic test to identify asymptomatic high-risk individuals with early stage lung cancer. EMBO Mol. Med. 2011, 3, 495–503, doi:10.1002/emmm.201100154.
[14]  Boeri, M.; Verri, C.; Conte, D.; Roz, L.; Modena, P.; Facchinetti, F.; Calabro, E.; Croce, C.M.; Pastorino, U.; Sozzi, G. MicroRNA signatures in tissues and plasma predict development and prognosis of computed tomography detected lung cancer. Proc. Natl. Acad. Sci. USA 2011, 108, 3713–3718, doi:10.1073/pnas.1100048108.
[15]  Chen, X.; Hu, Z.; Wang, W.; Ba, Y.; Ma, L.; Zhang, C.; Wang, C.; Ren, Z.; Zhao, Y.; Wu, S.; et al. Identification of ten serum microRNAs from a genome-wide serum microRNA expression profile as novel noninvasive biomarkers for nonsmall cell lung cancer diagnosis. Int. J. Cancer 2012, 130, 1620–1628, doi:10.1002/ijc.26177.
[16]  Hennessey, P.T.; Sanford, T.; Choudhary, A.; Mydlarz, W.W.; Brown, D.; Adai, A.T.; Ochs, M.F.; Ahrendt, S.A.; Mambo, E.; Califano, J.A. Serum microRNA biomarkers for detection of non-small cell lung cancer. PLoS One 2012, 7, doi:10.1371/journal.pone.0032307.
[17]  Zander, T.; Hofmann, A.; Staratschek-Jox, A.; Classen, S.; Debey-Pascher, S.; Maisel, D.; Ansen, S.; Hahn, M.; Beyer, M.; Thomas, R.K.; et al. Blood-based gene expression signatures in non-small cell lung cancer. Clin. Cancer Res. 2011, 17, 3360–3367, doi:10.1158/1078-0432.CCR-10-0533.
[18]  Bhattacharjee, A.; Richards, W.G.; Staunton, J.; Li, C.; Monti, S.; Vasa, P.; Ladd, C.; Beheshti, J.; Bueno, R.; Gillette, M.; et al. Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. Proc. Natl. Acad. Sci. USA 2001, 98, 13790–13795, doi:10.1073/pnas.191502998.
[19]  Inamura, K.; Fujiwara, T.; Hoshida, Y.; Isagawa, T.; Jones, M.H.; Virtanen, C.; Shimane, M.; Satoh, Y.; Okumura, S.; Nakagawa, K.; et al. Two subclasses of lung squamous cell carcinoma with different gene expression profiles and prognosis identified by hierarchical clustering and non-negative matrix factorization. Oncogene 2005, 24, 7105–7113, doi:10.1038/sj.onc.1208858.
[20]  Vosa, U.; Vooder, T.; Kolde, R.; Vilo, J.; Metspalu, A.; Annilo, T. Meta-analysis of microRNA expression in lung cancer. Int. J. Cancer 2013, 132, 2884–2893, doi:10.1002/ijc.27981.
[21]  Jang, J.S.; Simon, V.A.; Feddersen, R.M.; Rakhshan, F.; Schultz, D.A.; Zschunke, M.A.; Lingle, W.L.; Kolbert, C.P.; Jen, J. Quantitative miRNA expression analysis using fluidigm microfluidics dynamic arrays. BMC Genomics 2011, 12, doi:10.1186/1471-2164-12-144.
[22]  Pradervand, S.; Weber, J.; Lemoine, F.; Consales, F.; Paillusson, A.; Dupasquier, M.; Thomas, J.; Richter, H.; Kaessmann, H.; Beaudoing, E.; et al. Concordance among digital gene expression, microarrays, and qPCR when measuring differential expression of microRNAs. BioTechniques 2010, 48, 219–222, doi:10.2144/000113367.
[23]  Bediaga, N.G.; Davies, M.P.; Acha-Sagredo, A.; Hyde, R.; Raji, O.Y.; Page, R.; Walshaw, M.; Gosney, J.; Alfirevic, A.; Field, J.K.; et al. A microRNA-based prediction algorithm for diagnosis of non-small lung cell carcinoma in minimal biopsy material. Br. J. Cancer 2013, 109, 2404–2411, doi:10.1038/bjc.2013.623.
[24]  Bosse, Y.; Postma, D.S.; Sin, D.D.; Lamontagne, M.; Couture, C.; Gaudreault, N.; Joubert, P.; Wong, V.; Elliott, M.; van den Berge, M.; et al. Molecular signature of smoking in human lung tissues. Cancer Res. 2012, 72, 3753–3763, doi:10.1158/0008-5472.CAN-12-1160.
[25]  Beane, J.; Vick, J.; Schembri, F.; Anderlind, C.; Gower, A.; Campbell, J.; Luo, L.; Zhang, X.H.; Xiao, J.; Alekseyev, Y.O.; et al. Characterizing the impact of smoking and lung cancer on the airway transcriptome using RNA-Seq. Cancer Prev. Res. 2011, 4, 803–817, doi:10.1158/1940-6207.CAPR-11-0212.
[26]  Spira, A.; Beane, J.E.; Shah, V.; Steiling, K.; Liu, G.; Schembri, F.; Gilman, S.; Dumas, Y.M.; Calner, P.; Sebastiani, P.; et al. Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer. Nat. Med. 2007, 13, 361–366, doi:10.1038/nm1556.
[27]  Brothers, J.F.; Hijazi, K.; Mascaux, C.; El-Zein, R.A.; Spitz, M.R.; Spira, A. Bridging the clinical gaps: Genetic, epigenetic and transcriptomic biomarkers for the early detection of lung cancer in the post-National Lung Screening Trial era. BMC Med. 2013, 11, doi:10.1186/1741-7015-11-168.
[28]  Kahn, N.; Meister, M.; Eberhardt, R.; Muley, T.; Schnabel, P.A.; Bender, C.; Johannes, M.; Keitel, D.; Sultmann, H.; Herth, F.J.; et al. Early detection of lung cancer by molecular markers in endobronchial epithelial-lining fluid. J. Thoracic Oncol. 2012, 7, 1001–1008, doi:10.1097/JTO.0b013e31824fe921.
[29]  Leng, S.; Do, K.; Yingling, C.M.; Picchi, M.A.; Wolf, H.J.; Kennedy, T.C.; Feser, W.J.; Baron, A.E.; Franklin, W.A.; Brock, M.V.; et al. Defining a gene promoter methylation signature in sputum for lung cancer risk assessment. Clin. Cancer Res. 2012, 18, 3387–3395, doi:10.1158/1078-0432.CCR-11-3049.
[30]  Yu, L.; Todd, N.W.; Xing, L.; Xie, Y.; Zhang, H.; Liu, Z.; Fang, H.; Zhang, J.; Katz, R.L.; Jiang, F. Early detection of lung adenocarcinoma in sputum by a panel of microRNA markers. Int. J. Cancer 2010, 127, 2870–2878, doi:10.1002/ijc.25289.
[31]  Bajtarevic, A.; Ager, C.; Pienz, M.; Klieber, M.; Schwarz, K.; Ligor, M.; Ligor, T.; Filipiak, W.; Denz, H.; Fiegl, M.; et al. Noninvasive detection of lung cancer by analysis of exhaled breath. BMC Cancer 2009, 9, doi:10.1186/1471-2407-9-348.
[32]  Phillips, M.; Altorki, N.; Austin, J.H.; Cameron, R.B.; Cataneo, R.N.; Greenberg, J.; Kloss, R.; Maxfield, R.A.; Munawar, M.I.; Pass, H.I.; et al. Prediction of lung cancer using volatile biomarkers in breath. Canc. Biomarkers 2007, 3, 95–109.
[33]  Ulanowska, A.; Kowalkowski, T.; Trawinska, E.; Buszewski, B. The application of statistical methods using VOCs to identify patients with lung cancer. J. Breath Res. 2011, 5, doi:10.1088/1752-7155/5/4/046008.
[34]  McCulloch, M.; Turner, K.; Broffman, M. Lung cancer detection by canine scent: Will there be a lab in the lab? Eur. Respir. J. 2012, 39, 511–512, doi:10.1183/09031936.00215511.
[35]  Ettinger, D.S.; Akerley, W.; Borghaei, H.; Chang, A.C.; Cheney, R.T.; Chirieac, L.R.; D’Amico, T.A.; Demmy, T.L.; Ganti, A.K.; Govindan, R.; et al. Nccn, non-small cell lung cancer. J. Natl. Compr. Cancer Netw. 2012, 10, 1236–1271.
[36]  Kalemkerian, G.P.; Akerley, W.; Bogner, P.; Borghaei, H.; Chow, L.Q.; Downey, R.J.; Gandhi, L.; Ganti, A.K.; Govindan, R.; Grecula, J.C.; et al. Small cell lung cancer. J. Natl. Compr. Cancer Netw. 2013, 11, 78–98.
[37]  Molina, R.; Auge, J.M.; Bosch, X.; Escudero, J.M.; Vinolas, N.; Marrades, R.; Ramirez, J.; Carcereny, E.; Filella, X. Usefulness of serum tumor markers, including progastrin-releasing peptide, in patients with lung cancer: correlation with histology. Tumour Biol. 2009, 30, 121–129, doi:10.1159/000224628.
[38]  Torsetnes, S.B.; Nordlund, M.S.; Paus, E.; Halvorsen, T.G.; Reubsaet, L. Digging deeper into the field of the small cell lung cancer tumor marker ProGRP: A method for differentiation of its isoforms. J. Proteome Res. 2013, 12, 412–420, doi:10.1021/pr300751j.
[39]  Beer, D.G.; Kardia, S.L.; Huang, C.C.; Giordano, T.J.; Levin, A.M.; Misek, D.E.; Lin, L.; Chen, G.; Gharib, T.G.; Thomas, D.G.; et al. Gene-expression profiles predict survival of patients with lung adenocarcinoma. Nat. Med. 2002, 8, 816–824.
[40]  Garber, M.E.; Troyanskaya, O.G.; Schluens, K.; Petersen, S.; Thaesler, Z.; Pacyna-Gengelbach, M.; van de Rijn, M.; Rosen, G.D.; Perou, C.M.; Whyte, R.I.; et al. Diversity of gene expression in adenocarcinoma of the lung. Proc. Natl. Acad. Sci. USA 2001, 98, 13784–13789, doi:10.1073/pnas.241500798.
[41]  Hayes, D.N.; Monti, S.; Parmigiani, G.; Gilks, C.B.; Naoki, K.; Bhattacharjee, A.; Socinski, M.A.; Perou, C.; Meyerson, M. Gene expression profiling reveals reproducible human lung adenocarcinoma subtypes in multiple independent patient cohorts. J. Clin. Oncol. 2006, 24, 5079–5090, doi:10.1200/JCO.2005.05.1748.
[42]  Park, Y.Y.; Park, E.S.; Kim, S.B.; Kim, S.C.; Sohn, B.H.; Chu, I.S.; Jeong, W.; Mills, G.B.; Byers, L.A.; Lee, J.S. Development and validation of a prognostic gene-expression signature for lung adenocarcinoma. PLoS One 2012, 7, doi:10.1371/journal.pone.0044225.
[43]  Takeuchi, T.; Tomida, S.; Yatabe, Y.; Kosaka, T.; Osada, H.; Yanagisawa, K.; Mitsudomi, T.; Takahashi, T. Expression profile-defined classification of lung adenocarcinoma shows close relationship with underlying major genetic changes and clinicopathologic behaviors. J. Clin. Oncol. 2006, 24, 1679–1688, doi:10.1200/JCO.2005.03.8224.
[44]  Wilkerson, M.D.; Yin, X.; Walter, V.; Zhao, N.; Cabanski, C.R.; Hayward, M.C.; Miller, C.R.; Socinski, M.A.; Parsons, A.M.; Thorne, L.B.; et al. Differential pathogenesis of lung adenocarcinoma subtypes involving sequence mutations, copy number, chromosomal instability, and methylation. PLoS One 2012, 7, doi:10.1371/journal.pone.0036530.
[45]  Warth, A.; Muley, T.; Meister, M.; Stenzinger, A.; Thomas, M.; Schirmacher, P.; Schnabel, P.A.; Budczies, J.; Hoffmann, H.; Weichert, W. The novel histologic International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification system of lung adenocarcinoma is a stage-independent predictor of survival. J. Clin. Oncol. 2012, 30, 1438–1446, doi:10.1200/JCO.2011.37.2185.
[46]  Travis, W.D.; Brambilla, E.; Riely, G.J. New pathologic classification of lung cancer: Relevance for clinical practice and clinical trials. J. Clin. Oncol. 2013, 31, 992–1001, doi:10.1200/JCO.2012.46.9270.
[47]  Kadota, K.; Nitadori, J.; Sarkaria, I.S.; Sima, C.S.; Jia, X.; Yoshizawa, A.; Rusch, V.W.; Travis, W.D.; Adusumilli, P.S. Thyroid transcription factor-1 expression is an independent predictor of recurrence and correlates with the IASLC/ATS/ERS histologic classification in patients with stage I lung adenocarcinoma. Cancer 2013, 119, 931–938, doi:10.1002/cncr.27863.
[48]  Solis, L.M.; Behrens, C.; Raso, M.G.; Lin, H.Y.; Kadara, H.; Yuan, P.; Galindo, H.; Tang, X.; Lee, J.J.; Kalhor, N.; et al. Histologic patterns and molecular characteristics of lung adenocarcinoma associated with clinical outcome. Cancer 2012, 118, 2889–2899, doi:10.1002/cncr.26584.
[49]  Raponi, M.; Zhang, Y.; Yu, J.; Chen, G.; Lee, G.; Taylor, J.M.; Macdonald, J.; Thomas, D.; Moskaluk, C.; Wang, Y.; et al. Gene expression signatures for predicting prognosis of squamous cell and adenocarcinomas of the lung. Cancer Res. 2006, 66, 7466–7472, doi:10.1158/0008-5472.CAN-06-1191.
[50]  Wilkerson, M.D.; Yin, X.; Hoadley, K.A.; Liu, Y.; Hayward, M.C.; Cabanski, C.R.; Muldrew, K.; Miller, C.R.; Randell, S.H.; Socinski, M.A.; et al. Lung squamous cell carcinoma mRNA expression subtypes are reproducible, clinically important, and correspond to normal cell types. Clin. Cancer Res. 2010, 16, 4864–4875, doi:10.1158/1078-0432.CCR-10-0199.
[51]  The Cancer Genome Atlas Research Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature 2012, 489, 519–525, doi:10.1038/nature11404.
[52]  Wilkerson, M.D.; Schallheim, J.M.; Hayes, D.N.; Roberts, P.J.; Bastien, R.R.; Mullins, M.; Yin, X.; Miller, C.R.; Thorne, L.B.; Geiersbach, K.B.; et al. Prediction of lung cancer histological types by RT-qPCR gene expression in FFPE specimens. J. Mol. Diagn. 2013, 15, 485–497, doi:10.1016/j.jmoldx.2013.03.007.
[53]  Landi, M.T.; Zhao, Y.; Rotunno, M.; Koshiol, J.; Liu, H.; Bergen, A.W.; Rubagotti, M.; Goldstein, A.M.; Linnoila, I.; Marincola, F.M.; et al. MicroRNA expression differentiates histology and predicts survival of lung cancer. Clin. Cancer Res. 2010, 16, 430–441, doi:10.1158/1078-0432.CCR-09-1736.
[54]  Huang, W.; Hu, J.; Yang, D.W.; Fan, X.T.; Jin, Y.; Hou, Y.Y.; Wang, J.P.; Yuan, Y.F.; Tan, Y.S.; Zhu, X.Z.; et al. Two microRNA panels to discriminate three subtypes of lung carcinoma in bronchial brushing specimens. Am. J. Respir. Crit. Care Med. 2012, 186, 1160–1167, doi:10.1164/rccm.201203-0534OC.
[55]  Gilad, S.; Lithwick-Yanai, G.; Barshack, I.; Benjamin, S.; Krivitsky, I.; Edmonston, T.B.; Bibbo, M.; Thurm, C.; Horowitz, L.; Huang, Y.; et al. Classification of the four main types of lung cancer using a microRNA-based diagnostic assay. J. Mol. Diagn. 2012, 14, 510–517, doi:10.1016/j.jmoldx.2012.03.004.
[56]  Director’s Challenge Consortium for the Molecular Classification of Lung Adenocarcinoma; Shedden, K.; Taylor, J.M.; Enkemann, S.A.; Tsao, M.S.; Yeatman, T.J.; Gerald, W.L.; Eschrich, S.; Jurisica, I.; Giordano, T.J.; et al. Gene expression-based survival prediction in lung adenocarcinoma: A multi-site, blinded validation study. Nat. Med. 2008, 14, 822–827, doi:10.1038/nm.1790.
[57]  Larsen, J.E.; Pavey, S.J.; Passmore, L.H.; Bowman, R.V.; Hayward, N.K.; Fong, K.M. Gene expression signature predicts recurrence in lung adenocarcinoma. Clin. Cancer Res. 2007, 13, 2946–2954, doi:10.1158/1078-0432.CCR-06-2525.
[58]  Li, Y.; Tang, H.; Sun, Z.; Bungum, A.O.; Edell, E.S.; Lingle, W.L.; Stoddard, S.M.; Zhang, M.; Jen, J.; Yang, P.; et al. Network-based approach identified cell cycle genes as predictor of overall survival in lung adenocarcinoma patients. Lung Cancer 2013, 80, 91–98, doi:10.1016/j.lungcan.2012.12.022.
[59]  Tomida, S.; Takeuchi, T.; Shimada, Y.; Arima, C.; Matsuo, K.; Mitsudomi, T.; Yatabe, Y.; Takahashi, T. Relapse-related molecular signature in lung adenocarcinomas identifies patients with dismal prognosis. J. Clin. Oncol. 2009, 27, 2793–2799, doi:10.1200/JCO.2008.19.7053.
[60]  Larsen, J.E.; Pavey, S.J.; Passmore, L.H.; Bowman, R.; Clarke, B.E.; Hayward, N.K.; Fong, K.M. Expression profiling defines a recurrence signature in lung squamous cell carcinoma. Carcinogenesis 2007, 28, 760–766.
[61]  Botling, J.; Edlund, K.; Lohr, M.; Hellwig, B.; Holmberg, L.; Lambe, M.; Berglund, A.; Ekman, S.; Bergqvist, M.; Ponten, F.; et al. Biomarker discovery in non-small cell lung cancer: Integrating gene expression profiling, meta-analysis, and tissue microarray validation. Clin. Cancer Res. 2013, 19, 194–204, doi:10.1158/1078-0432.CCR-12-1139.
[62]  Hou, J.; Aerts, J.; den Hamer, B.; van Ijcken, W.; den Bakker, M.; Riegman, P.; van der Leest, C.; van der Spek, P.; Foekens, J.A.; Hoogsteden, H.C.; et al. Gene expression-based classification of non-small cell lung carcinomas and survival prediction. PLoS One 2010, 5, doi:10.1371/journal.pone.0010312.
[63]  Mitra, R.; Lee, J.; Jo, J.; Milani, M.; McClintick, J.N.; Edenberg, H.J.; Kesler, K.A.; Rieger, K.M.; Badve, S.; Cummings, O.W.; et al. Prediction of postoperative recurrence-free survival in non-small cell lung cancer by using an internationally validated gene expression model. Clin. Cancer Res. 2011, 17, 2934–2946, doi:10.1158/1078-0432.CCR-10-1803.
[64]  Roepman, P.; Jassem, J.; Smit, E.F.; Muley, T.; Niklinski, J.; van de Velde, T.; Witteveen, A.T.; Rzyman, W.; Floore, A.; Burgers, S.; et al. An immune response enriched 72-gene prognostic profile for early-stage non-small-cell lung cancer. Clin. Cancer Res. 2009, 15, 284–290, doi:10.1158/1078-0432.CCR-08-1258.
[65]  Xie, Y.; Xiao, G.; Coombes, K.R.; Behrens, C.; Solis, L.M.; Raso, G.; Girard, L.; Erickson, H.S.; Roth, J.; Heymach, J.V.; et al. Robust gene expression signature from formalin-fixed paraffin-embedded samples predicts prognosis of non-small-cell lung cancer patients. Clin. Cancer Res. 2011, 17, 5705–5714, doi:10.1158/1078-0432.CCR-11-0196.
[66]  Zhu, C.Q.; Ding, K.; Strumpf, D.; Weir, B.A.; Meyerson, M.; Pennell, N.; Thomas, R.K.; Naoki, K.; Ladd-Acosta, C.; Liu, N.; et al. Prognostic and predictive gene signature for adjuvant chemotherapy in resected non-small-cell lung cancer. J. Clin. Oncol. 2010, 28, 4417–4424, doi:10.1200/JCO.2009.26.4325.
[67]  Lee, E.S.; Son, D.S.; Kim, S.H.; Lee, J.; Jo, J.; Han, J.; Kim, H.; Lee, H.J.; Choi, H.Y.; Jung, Y.; et al. Prediction of recurrence-free survival in postoperative non-small cell lung cancer patients by using an integrated model of clinical information and gene expression. Clin. Cancer Res. 2008, 14, 7397–7404, doi:10.1158/1078-0432.CCR-07-4937.
[68]  Boutros, P.C.; Lau, S.K.; Pintilie, M.; Liu, N.; Shepherd, F.A.; Der, S.D.; Tsao, M.S.; Penn, L.Z.; Jurisica, I. Prognostic gene signatures for non-small-cell lung cancer. Proc. Natl. Acad. Sci. USA 2009, 106, 2824–2828, doi:10.1073/pnas.0809444106.
[69]  Chen, D.T.; Hsu, Y.L.; Fulp, W.J.; Coppola, D.; Haura, E.B.; Yeatman, T.J.; Cress, W.D. Prognostic and predictive value of a malignancy-risk gene signature in early-stage non-small cell lung cancer. J. Natl. Cancer Instit. 2011, 103, 1859–1870, doi:10.1093/jnci/djr420.
[70]  Guo, N.L.; Wan, Y.W.; Tosun, K.; Lin, H.; Msiska, Z.; Flynn, D.C.; Remick, S.C.; Vallyathan, V.; Dowlati, A.; Shi, X.; et al. Confirmation of gene expression-based prediction of survival in non-small cell lung cancer. Clin. Cancer Res. 2008, 14, 8213–8220, doi:10.1158/1078-0432.CCR-08-0095.
[71]  Lu, Y.; Lemon, W.; Liu, P.Y.; Yi, Y.; Morrison, C.; Yang, P.; Sun, Z.; Szoke, J.; Gerald, W.L.; Watson, M.; et al. A gene expression signature predicts survival of patients with stage I non-small cell lung cancer. PLoS Med. 2006, 3, doi:10.1371/journal.pmed.0030467.
[72]  Lu, Y.; Wang, L.; Liu, P.; Yang, P.; You, M. Gene-expression signature predicts postoperative recurrence in stage I non-small cell lung cancer patients. PLoS One 2012, 7, doi:10.1371/journal.pone.0030880.
[73]  Sun, Z.; Wigle, D.A.; Yang, P. Non-overlapping and non-cell-type-specific gene expression signatures predict lung cancer survival. J. Clin. Oncol. 2008, 26, 877–883, doi:10.1200/JCO.2007.13.1516.
[74]  Van Laar, R.K. Genomic signatures for predicting survival and adjuvant chemotherapy benefit in patients with non-small-cell lung cancer. BMC Med. Genomics 2012, 5, doi:10.1186/1755-8794-5-30.
[75]  Akagi, I.; Okayama, H.; Schetter, A.J.; Robles, A.I.; Kohno, T.; Bowman, E.D.; Kazandjian, D.; Welsh, J.A.; Oue, N.; Saito, M.; et al. Combination of protein coding and noncoding gene expression as a robust prognostic classifier in stage I lung adenocarcinoma. Cancer Res. 2013, 73, 3821–3832, doi:10.1158/0008-5472.CAN-13-0031.
[76]  Bianchi, F.; Nuciforo, P.; Vecchi, M.; Bernard, L.; Tizzoni, L.; Marchetti, A.; Buttitta, F.; Felicioni, L.; Nicassio, F.; di Fiore, P.P. Survival prediction of stage I lung adenocarcinomas by expression of 10 genes. J. Clin. Investig. 2007, 117, 3436–3444, doi:10.1172/JCI32007.
[77]  Chen, H.Y.; Yu, S.L.; Chen, C.H.; Chang, G.C.; Chen, C.Y.; Yuan, A.; Cheng, C.L.; Wang, C.H.; Terng, H.J.; Kao, S.F.; et al. A five-gene signature and clinical outcome in non-small-cell lung cancer. N. Engl. J. Med. 2007, 356, 11–20, doi:10.1056/NEJMoa060096.
[78]  Lau, S.K.; Boutros, P.C.; Pintilie, M.; Blackhall, F.H.; Zhu, C.Q.; Strumpf, D.; Johnston, M.R.; Darling, G.; Keshavjee, S.; Waddell, T.K.; et al. Three-gene prognostic classifier for early-stage non small-cell lung cancer. J. Clin. Oncol. 2007, 25, 5562–5569, doi:10.1200/JCO.2007.12.0352.
[79]  Raz, D.J.; Ray, M.R.; Kim, J.Y.; He, B.; Taron, M.; Skrzypski, M.; Segal, M.; Gandara, D.R.; Rosell, R.; Jablons, D.M. A multigene assay is prognostic of survival in patients with early-stage lung adenocarcinoma. Clin. Cancer Res. 2008, 14, 5565–5570, doi:10.1158/1078-0432.CCR-08-0544.
[80]  Seike, M.; Yanaihara, N.; Bowman, E.D.; Zanetti, K.A.; Budhu, A.; Kumamoto, K.; Mechanic, L.E.; Matsumoto, S.; Yokota, J.; Shibata, T.; et al. Use of a cytokine gene expression signature in lung adenocarcinoma and the surrounding tissue as a prognostic classifier. J. Natl. Cancer Instit. 2007, 99, 1257–1269, doi:10.1093/jnci/djm083.
[81]  Wistuba, I.I.; Behrens, C.; Lombardi, F.; Wagner, S.; Fujimoto, J.; Raso, M.G.; Spaggiari, L.; Galetta, D.; Riley, R.; Hughes, E.; et al. Validation of a proliferation-based expression signature as prognostic marker in early stage lung adenocarcinoma. Clin. Cancer Res. 2013, 19, 6261–6271, doi:10.1158/1078-0432.CCR-13-0596.
[82]  Skrzypski, M.; Jassem, E.; Taron, M.; Sanchez, J.J.; Mendez, P.; Rzyman, W.; Gulida, G.; Raz, D.; Jablons, D.; Provencio, M.; et al. Three-gene expression signature predicts survival in early-stage squamous cell carcinoma of the lung. Clin. Cancer Res. 2008, 14, 4794–4799, doi:10.1158/1078-0432.CCR-08-0576.
[83]  Kratz, J.R.; He, J.; van den Eeden, S.K.; Zhu, Z.H.; Gao, W.; Pham, P.T.; Mulvihill, M.S.; Ziaei, F.; Zhang, H.; Su, B.; et al. A practical molecular assay to predict survival in resected non-squamous, non-small-cell lung cancer: Development and international validation studies. Lancet 2012, 379, 823–832, doi:10.1016/S0140-6736(11)61941-7.
[84]  Lu, Y.; Govindan, R.; Wang, L.; Liu, P.Y.; Goodgame, B.; Wen, W.; Sezhiyan, A.; Pfeifer, J.; Li, Y.F.; Hua, X.; et al. MicroRNA profiling and prediction of recurrence/relapse-free survival in stage I lung cancer. Carcinogenesis 2012, 33, 1046–1054, doi:10.1093/carcin/bgs100.
[85]  Yanaihara, N.; Caplen, N.; Bowman, E.; Seike, M.; Kumamoto, K.; Yi, M.; Stephens, R.M.; Okamoto, A.; Yokota, J.; Tanaka, T.; et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 2006, 9, 189–198, doi:10.1016/j.ccr.2006.01.025.
[86]  Yu, S.L.; Chen, H.Y.; Chang, G.C.; Chen, C.Y.; Chen, H.W.; Singh, S.; Cheng, C.L.; Yu, C.J.; Lee, Y.C.; Chen, H.S.; et al. MicroRNA signature predicts survival and relapse in lung cancer. Cancer Cell 2008, 13, 48–57, doi:10.1016/j.ccr.2007.12.008.
[87]  Voortman, J.; Goto, A.; Mendiboure, J.; Sohn, J.J.; Schetter, A.J.; Saito, M.; Dunant, A.; Pham, T.C.; Petrini, I.; Lee, A.; et al. MicroRNA expression and clinical outcomes in patients treated with adjuvant chemotherapy after complete resection of non-small cell lung carcinoma. Cancer Res. 2010, 70, 8288–8298, doi:10.1158/0008-5472.CAN-10-1348.
[88]  Hu, Z.; Chen, X.; Zhao, Y.; Tian, T.; Jin, G.; Shu, Y.; Chen, Y.; Xu, L.; Zen, K.; Zhang, C.; et al. Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. J. Clin. Oncol. 2010, 28, 1721–1726, doi:10.1200/JCO.2009.24.9342.
[89]  Kaduthanam, S.; Gade, S.; Meister, M.; Brase, J.C.; Johannes, M.; Dienemann, H.; Warth, A.; Schnabel, P.A.; Herth, F.J.; Sultmann, H.; et al. Serum miR-142-3p is associated with early relapse in operable lung adenocarcinoma patients. Lung Cancer 2013, 80, 223–227, doi:10.1016/j.lungcan.2013.01.013.
[90]  Sanfiorenzo, C.; Ilie, M.I.; Belaid, A.; Barlesi, F.; Mouroux, J.; Marquette, C.H.; Brest, P.; Hofman, P. Two panels of plasma microRNAs as non-invasive biomarkers for prediction of recurrence in resectable NSCLC. PLoS One 2013, 8, doi:10.1371/journal.pone.0054596.
[91]  Wang, Y.; Gu, J.; Roth, J.A.; Hildebrandt, M.A.; Lippman, S.M.; Ye, Y.; Minna, J.D.; Wu, X. Pathway-based serum microRNA profiling and survival in patients with advanced stage non-small cell lung cancer. Cancer Res. 2013, 73, 4801–4809, doi:10.1158/0008-5472.CAN-12-3273.
[92]  Besse, B.; Olaussen, K.A.; Soria, J.C. ERCC1 and RRM1: Ready for prime time? J. Clin. Oncol. 2013, 31, 1050–1060, doi:10.1200/JCO.2012.43.0900.
[93]  Friboulet, L.; Olaussen, K.A.; Pignon, J.P.; Shepherd, F.A.; Tsao, M.S.; Graziano, S.; Kratzke, R.; Douillard, J.Y.; Seymour, L.; Pirker, R.; et al. ERCC1 isoform expression and DNA repair in non-small-cell lung cancer. N. Engl. J. Med. 2013, 368, 1101–1110, doi:10.1056/NEJMoa1214271.
[94]  Jakobsen, J.N.; Santoni-Rugiu, E.; Ravn, J.; Sorensen, J.B. Intratumour variation of biomarker expression by immunohistochemistry in resectable non-small cell lung cancer. Eur. J. Cancer 2013, doi:10.1016/j.ejca.2013.04.003.
[95]  Graziano, S.L.; Lacas, B.; Vollmer, R.; Kratzke, R.; Popper, H.; Filipits, M.; Seymour, L.; Shepherd, F.A.; Rosell, R.; Veillard, A.S.; et al. Cross-validation analysis of the prognostic significance of mucin expression in patients with resected non-small cell lung cancer treated with adjuvant chemotherapy: Results from IALT, JBR.10 and ANITA. Lung Cancer 2013, 82, 149–155, doi:10.1016/j.lungcan.2013.06.015.
[96]  Shepherd, F.A.; Domerg, C.; Hainaut, P.; Janne, P.A.; Pignon, J.P.; Graziano, S.; Douillard, J.Y.; Brambilla, E.; le Chevalier, T.; Seymour, L.; et al. Pooled analysis of the prognostic and predictive effects of KRAS mutation status and KRAS mutation subtype in early-stage resected non-small-cell lung cancer in four trials of adjuvant chemotherapy. J. Clin. Oncol. 2013, 31, 2173–2181, doi:10.1200/JCO.2012.48.1390.
[97]  Edelman, M.J.; Schneider, C.P.; Tsai, C.M.; Kim, H.T.; Quoix, E.; Luft, A.V.; Kaleta, R.; Mukhopadhyay, P.; Trifan, O.C.; Whitaker, L.; et al. Randomized phase II study of ixabepilone or paclitaxel plus carboplatin in patients with non-small-cell lung cancer prospectively stratified by beta-3 tubulin status. J. Clin. Oncol. 2013, 31, 1990–1996, doi:10.1200/JCO.2012.45.3282.
[98]  Holdenrieder, S.; von Pawel, J.; Dankelmann, E.; Duell, T.; Faderl, B.; Markus, A.; Siakavara, M.; Wagner, H.; Feldmann, K.; Hoffmann, H.; et al. Nucleosomes, ProGRP, NSE, CYFRA 21-1, and CEA in monitoring first-line chemotherapy of small cell lung cancer. Clin. Cancer Res. 2008, 14, 7813–7821, doi:10.1158/1078-0432.CCR-08-0678.
[99]  Tang, H.; Xiao, G.; Behrens, C.; Schiller, J.; Allen, J.; Chow, C.W.; Suraokar, M.; Corvalan, A.; Mao, J.; White, M.A.; et al. A 12-gene set predicts survival benefits from adjuvant chemotherapy in non-small cell lung cancer patients. Clin. Cancer Res. 2013, 19, 1577–1586, doi:10.1158/1078-0432.CCR-12-2321.
[100]  Chai, Y.; Lam, R.K.; Calaf, G.M.; Zhou, H.; Amundson, S.; Hei, T.K. Radiation-induced non-targeted response in vivo: Role of the TGFbeta-TGFBR1-COX-2 signalling pathway. Br. J. Cancer 2013, 108, 1106–1112, doi:10.1038/bjc.2013.53.
[101]  Yuan, S.T.; Ellingrod, V.L.; Schipper, M.; Stringer, K.A.; Cai, X.; Hayman, J.A.; Yu, J.; Lawrence, T.S.; Kong, F.M. Genetic variations in TGFbeta1, tPA, and ACE and radiation-induced thoracic toxicities in patients with non-small-cell lung cancer. J. Thoracic Oncol. 2013, 8, 208–213, doi:10.1097/JTO.0b013e318274592e.
[102]  Niu, N.; Qin, Y.; Fridley, B.L.; Hou, J.; Kalari, K.R.; Zhu, M.; Wu, T.Y.; Jenkins, G.D.; Batzler, A.; Wang, L. Radiation pharmacogenomics: A genome-wide association approach to identify radiation response biomarkers using human lymphoblastoid cell lines. Genome Res. 2010, 20, 1482–1492, doi:10.1101/gr.107672.110.
[103]  Torres-Roca, J.F.; Eschrich, S.; Zhao, H.; Bloom, G.; Sung, J.; McCarthy, S.; Cantor, A.B.; Scuto, A.; Li, C.; Zhang, S.; et al. Prediction of radiation sensitivity using a gene expression classifier. Cancer Res. 2005, 65, 7169–7176, doi:10.1158/0008-5472.CAN-05-0656.
[104]  Dehing-Oberije, C.; Aerts, H.; Yu, S.; de Ruysscher, D.; Menheere, P.; Hilvo, M.; van der Weide, H.; Rao, B.; Lambin, P. Development and validation of a prognostic model using blood biomarker information for prediction of survival of non-small-cell lung cancer patients treated with combined chemotherapy and radiation or radiotherapy alone (NCT00181519, NCT00573040, and NCT00572325). Int. J. Radiat. Oncol. Biol. Phys. 2011, 81, 360–368, doi:10.1016/j.ijrobp.2010.06.011.
[105]  Ono, A.; Naito, T.; Ito, I.; Watanabe, R.; Shukuya, T.; Kenmotsu, H.; Tsuya, A.; Nakamura, Y.; Murakami, H.; Kaira, K.; et al. Correlations between serial pro-gastrin-releasing peptide and neuron-specific enolase levels, and the radiological response to treatment and survival of patients with small-cell lung cancer. Lung Cancer 2012, 76, 439–444, doi:10.1016/j.lungcan.2011.12.012.
[106]  Koh, P.K.; Faivre-Finn, C.; Blackhall, F.H.; de Ruysscher, D. Targeted agents in non-small cell lung cancer (NSCLC): Clinical developments and rationale for the combination with thoracic radiotherapy. Cancer Treatm. Rev. 2012, 38, 626–640, doi:10.1016/j.ctrv.2011.11.003.
[107]  Das, A.K.; Chen, B.P.; Story, M.D.; Sato, M.; Minna, J.D.; Chen, D.J.; Nirodi, C.S. Somatic mutations in the tyrosine kinase domain of epidermal growth factor receptor (EGFR) abrogate EGFR-mediated radioprotection in non-small cell lung carcinoma. Cancer Res. 2007, 67, 5267–5274, doi:10.1158/0008-5472.CAN-07-0242.
[108]  Wang, M.; Morsbach, F.; Sander, D.; Gheorghiu, L.; Nanda, A.; Benes, C.; Kriegs, M.; Krause, M.; Dikomey, E.; Baumann, M.; et al. EGF receptor inhibition radiosensitizes NSCLC cells by inducing senescence in cells sustaining DNA double-strand breaks. Cancer Res. 2011, 71, 6261–6269, doi:10.1158/0008-5472.CAN-11-0213.
[109]  Contessa, J.N.; Hampton, J.; Lammering, G.; Mikkelsen, R.B.; Dent, P.; Valerie, K.; Schmidt-Ullrich, R.K. Ionizing radiation activates Erb-B receptor dependent Akt and p70 S6 kinase signaling in carcinoma cells. Oncogene 2002, 21, 4032–4041, doi:10.1038/sj.onc.1205500.
[110]  Ulloa-Montoya, F.; Louahed, J.; Dizier, B.; Gruselle, O.; Spiessens, B.; Lehmann, F.F.; Suciu, S.; Kruit, W.H.; Eggermont, A.M.; Vansteenkiste, J.; et al. Predictive gene signature in MAGE-A3 antigen-specific cancer immunotherapy. J. Clin. Oncol. 2013, 31, 2388–2395, doi:10.1200/JCO.2012.44.3762.
[111]  Galon, J.; Angell, H.K.; Bedognetti, D.; Marincola, F.M. The continuum of cancer immunosurveillance: Prognostic, predictive, and mechanistic signatures. Immunity 2013, 39, 11–26, doi:10.1016/j.immuni.2013.07.008.
[112]  Morse, M.A.; Osada, T.; Hobeika, A.; Patel, S.; Lyerly, H.K. Biomarkers and correlative endpoints for immunotherapy trials. Am. Soc. Clin. Oncol. Educ. Book 2013, 2013, 287–293.
[113]  Pikor, L.A.; Ramnarine, V.R.; Lam, S.; Lam, W.L. Genetic alterations defining NSCLC subtypes and their therapeutic implications. Lung Cancer 2013, 82, 179–189, doi:10.1016/j.lungcan.2013.07.025.
[114]  Cagle, P.T.; Sholl, L.M.; Lindeman, N.I.; Alsabeh, R.; Divaris, D.X.; Foulis, P.; Lee, G.; Neal, J.W.; Nowak, J.A.; Yu, P.P. Template for reporting results of biomarker testing of specimens from patients with non-small cell carcinoma of the lung. Arch. Pathol. Lab. Med. 2013, doi:10.5858/arpa.2011.0232-CP.
[115]  Neal, J.W.; Sequist, L.V. Targeted therapies: Optimal first-line therapy for NSCLC with EGFR mutations. Nat. Rev. Clin. Oncol. 2010, 7, 71–72, doi:10.1038/nrclinonc.2009.191.
[116]  Shaw, A.T.; Yeap, B.Y.; Solomon, B.J.; Riely, G.J.; Gainor, J.; Engelman, J.A.; Shapiro, G.I.; Costa, D.B.; Ou, S.H.; Butaney, M.; et al. Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: A retrospective analysis. Lancet Oncol. 2011, 12, 1004–1012, doi:10.1016/S1470-2045(11)70232-7.
[117]  Mao, C.; Qiu, L.X.; Liao, R.Y.; Du, F.B.; Ding, H.; Yang, W.C.; Li, J.; Chen, Q. KRAS mutations and resistance to EGFR-TKIs treatment in patients with non-small cell lung cancer: A meta-analysis of 22 studies. Lung Cancer 2010, 69, 272–278, doi:10.1016/j.lungcan.2009.11.020.
[118]  Pao, W.; Wang, T.Y.; Riely, G.J.; Miller, V.A.; Pan, Q.; Ladanyi, M.; Zakowski, M.F.; Heelan, R.T.; Kris, M.G.; Varmus, H.E. KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med. 2005, 2, doi:10.1371/journal.pmed.0020017.
[119]  Laurie, S.A.; Goss, G.D. Role of epidermal growth factor receptor inhibitors in epidermal growth factor receptor wild-type non-small-cell lung cancer. J. Clin. Oncol. 2013, 31, 1061–1069, doi:10.1200/JCO.2012.43.4522.
[120]  Carbone, D.P.; Ding, K.; Roder, H.; Grigorieva, J.; Roder, J.; Tsao, M.S.; Seymour, L.; Shepherd, F.A. Prognostic and predictive role of the VeriStrat plasma test in patients with advanced non-small-cell lung cancer treated with erlotinib or placebo in the NCIC Clinical Trials Group BR.21 trial. J. Thoracic Oncol. 2012, 7, 1653–1660, doi:10.1097/JTO.0b013e31826c1155.
[121]  Martini, M.; Vecchione, L.; Siena, S.; Tejpar, S.; Bardelli, A. Targeted therapies: How personal should we go? Nat. Rev. Clin. Oncol. 2012, 9, 87–97.
[122]  Sequist, L.V.; Waltman, B.A.; Dias-Santagata, D.; Digumarthy, S.; Turke, A.B.; Fidias, P.; Bergethon, K.; Shaw, A.T.; Gettinger, S.; Cosper, A.K.; et al. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci. Transl. Med. 2013, 7, 75ra26, doi:10.1126/scitranslmed.3002003.
[123]  Byers, L.A.; Diao, L.; Wang, J.; Saintigny, P.; Girard, L.; Peyton, M.; Shen, L.; Fan, Y.; Giri, U.; Tumula, P.K.; et al. An epithelial-mesenchymal transition gene signature predicts resistance to EGFR and PI3K inhibitors and identifies Axl as a therapeutic target for overcoming EGFR inhibitor resistance. Clin. Cancer Res. 2013, 19, 279–290, doi:10.1158/1078-0432.CCR-12-1558.
[124]  Blumenschein, G.R.; Saintigny, P.; Liu, S.; Kim, E.S.; Tsao, A.S.; Herbst, R.; Alden, C.M.; Lee, J.J.; Tang, X.; Stewart, D.J.; et al. Comprehensive biomarker analysis and final efficacy results of sorafenib in the BATTLE (Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination) trial. Clin. Cancer Res. 2013, doi:10.1158/1078-0432.CCR-12-1818.
[125]  Okayama, H.; Kohno, T.; Ishii, Y.; Shimada, Y.; Shiraishi, K.; Iwakawa, R.; Furuta, K.; Tsuta, K.; Shibata, T.; Yamamoto, S.; et al. Identification of genes upregulated in ALK-positive and EGFR/KRAS/ALK-negative lung adenocarcinomas. Cancer Res. 2012, 72, 100–111, doi:10.1158/0008-5472.CAN-11-1403.
[126]  Chitale, D.; Gong, Y.; Taylor, B.S.; Broderick, S.; Brennan, C.; Somwar, R.; Golas, B.; Wang, L.; Motoi, N.; Szoke, J.; et al. An integrated genomic analysis of lung cancer reveals loss of DUSP4 in EGFR-mutant tumors. Oncogene 2009, 28, 2773–2783, doi:10.1038/onc.2009.135.
[127]  Ettinger, D.S.; Akerley, W.; Borghaei, H.; Chang, A.C.; Cheney, R.T.; Chirieac, L.R.; D’Amico, T.A.; Demmy, T.L.; Govindan, R.; Grannis, F.W.; et al. Non-small cell lung cancer, version 2.2013. J. Natl. Compr. Cancer Netw. 2013, 11, 645–653.
[128]  Muller, B.M.; Keil, E.; Lehmann, A.; Winzer, K.J.; Richter-Ehrenstein, C.; Prinzler, J.; Bangemann, N.; Reles, A.; Stadie, S.; Schoenegg, W.; et al. The endopredict gene-expression assay in clinical practice–performance and impact on clinical decisions. PLoS One 2013, 8, doi:10.1371/journal.pone.0068252.
[129]  Rouzier, R.; Pronzato, P.; Chereau, E.; Carlson, J.; Hunt, B.; Valentine, W.J. Multigene assays and molecular markers in breast cancer: Systematic review of health economic analyses. Breast Cancer Res. Treatm. 2013, 139, 621–637, doi:10.1007/s10549-013-2559-1.
[130]  Azim, H.A., Jr.; Michiels, S.; Zagouri, F.; Delaloge, S.; Filipits, M.; Namer, M.; Neven, P.; Symmans, W.F.; Thompson, A.; Andre, F.; et al. Utility of prognostic genomic tests in breast cancer practice: The IMPAKT 2012 Working Group Consensus Statement. Ann. Oncol. 2013, 24, 647–654, doi:10.1093/annonc/mds645.
[131]  Subramanian, J.; Simon, R. Gene expression-based prognostic signatures in lung cancer: Ready for clinical use? J. Natl. Cancer Instit. 2010, 102, 464–474.
[132]  Bild, A.H.; Yao, G.; Chang, J.T.; Wang, Q.; Potti, A.; Chasse, D.; Joshi, M.B.; Harpole, D.; Lancaster, J.M.; Berchuck, A.; et al. Oncogenic pathway signatures in human cancers as a guide to targeted therapies. Nature 2006, 439, 353–357.
[133]  Ding, L.; Getz, G.; Wheeler, D.A.; Mardis, E.R.; McLellan, M.D.; Cibulskis, K.; Sougnez, C.; Greulich, H.; Muzny, D.M.; Morgan, M.B.; et al. Somatic mutations affect key pathways in lung adenocarcinoma. Nature 2008, 455, 1069–1075, doi:10.1038/nature07423.

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133