Skip to main content
SpringerLink
Log in

Molecular classification of non-small-cell lung cancer: diagnosis, individualized treatment, and prognosis

  • Review
  • Published:
Frontiers of Medicine Aims and scope Submit manuscript

Abstract

Non-small-cell lung cancer (NSCLC) is the most common cause of premature death among the malignant diseases worldwide. The current staging criteria do not fully capture the complexity of this disease. Molecular biology techniques, particularly gene expression microarrays, proteomics, and next-generation sequencing, have recently been developed to facilitate effectively its molecular classification. The underlying etiology, pathogenesis, therapeutics, and prognosis of NSCLC based on an improved molecular classification scheme may promote individualized treatment and improve clinical outcomes. This review focuses on the molecular classification of NSCLC based on gene expression microarray technology reported during the past decade, as well as their applications for improving the diagnosis, staging and treatment of NSCLC, including the discovery of prognostic markers or potential therapeutic targets. We highlight some of the recent studies that may refine the identification of NSCLC subtypes using novel techniques such as epigenetics, proteomics, or deep sequencing.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Capelletto E, Novello S. Emerging new agents for the management of patients with non-small cell lung cancer. Drugs 2012; 72(Suppl 1): 37–52

    Article  PubMed  CAS  Google Scholar 

  2. Singhal S, Miller D, Ramalingam S, Sun SY. Gene expression profiling of non-small cell lung cancer. Lung Cancer 2008; 60(3): 313–324

    Article  PubMed  Google Scholar 

  3. Travis WD, Brambilla E, Müller-Hermeling HK, Harris CC. Tumours of the lung. In: World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart. Lyon: IARC Press, 2004:10

    Google Scholar 

  4. Lee HJ, Lee CH, Jeong YJ, Chung DH, Goo JM, Park CM, Austin JH. IASLC/ATS/ERS International Multidisciplinary Classification of Lung Adenocarcinoma: novel concepts and radiologic implications. J Thorac Imaging 2012; 27(6): 340–353

    Article  PubMed  Google Scholar 

  5. Duncavage E, Goodgame B, Sezhiyan A, Govindan R, Pfeifer J. Use of microRNA expression levels to predict outcomes in resected stage I non-small cell lung cancer. J Thorac Oncol 2010; 5(11): 1755–1763

    Article  PubMed  Google Scholar 

  6. National Cancer Institute. Director’s challenge: toward a molecular classification of tumors. http://grants.nih.gov/grants/guide/rfa-files/RFA-CA-98-027.html (Accessed on October 24, 2012)

  7. Shibata T, Uryu S, Kokubu A, Hosoda F, Ohki M, Sakiyama T, Matsuno Y, Tsuchiya R, Kanai Y, Kondo T, Imoto I, Inazawa J, Hirohashi S. Genetic classification of lung adenocarcinoma based on array-based comparative genomic hybridization analysis: its association with clinicopathologic features. Clin Cancer Res 2005; 11(17): 6177–6185

    Article  PubMed  CAS  Google Scholar 

  8. Gordon GJ, Jensen RV, Hsiao LL, Gullans SR, Blumenstock JE, Ramaswamy S, Richards WG, Sugarbaker DJ, Bueno R. Translation of microarray data into clinically relevant cancer diagnostic tests using gene expression ratios in lung cancer and mesothelioma. Cancer Res 2002; 62(17): 4963–4967

    PubMed  CAS  Google Scholar 

  9. Nonami Y, Ohtuki Y, Sasaguri S. Study of the diagnostic difference between the clinical diagnostic criteria and results of immunohistochemical staining of multiple primary lung cancers. J Cardiovasc Surg (Torino) 2003; 44(5): 661–665

    CAS  Google Scholar 

  10. Arai J, Tsuchiya T, Oikawa M, Mochinaga K, Hayashi T, Yoshiura K, Tsukamoto K, Yamasaki N, Matsumoto K, Miyazaki T, Nagayasu T. Clinical and molecular analysis of synchronous double lung cancers. Lung Cancer 2012; 77(2): 281–287

    Article  PubMed  Google Scholar 

  11. Girard N, Deshpande C, Azzoli CG, Rusch VW, Travis WD, Ladanyi M, Pao W. Use of epidermal growth factor receptor/Kirsten rat sarcoma 2 viral oncogene homolog mutation testing to define clonal relationships among multiple lung adenocarcinomas: comparison with clinical guidelines. Chest 2010; 137(1): 46–52

    Article  PubMed  CAS  Google Scholar 

  12. Giordano TJ, Shedden KA, Schwartz DR, Kuick R, Taylor JM, Lee N, Misek DE, Greenson JK, Kardia SL, Beer DG, Rennert G, Cho KR, Gruber SB, Fearon ER, Hanash S. Organ-specific molecular classification of primary lung, colon, and ovarian adenocarcinomas using gene expression profiles. Am J Pathol 2001; 159(4): 1231–1238

    Article  PubMed  CAS  Google Scholar 

  13. Sørensen JB, Hirsch FR, Gazdar A, Olsen JE. Interobserver variability in histopathologic subtyping and grading of pulmonary adenocarcinoma. Cancer 1993; 71(10): 2971–2976

    Article  PubMed  Google Scholar 

  14. Garber ME, Troyanskaya OG, Schluens K, Petersen S, Thaesler Z, Pacyna-Gengelbach M, van de Rijn M, Rosen GD, Perou CM, Whyte RI, Altman RB, Brown PO, Botstein D, Petersen I. Diversity of gene expression in adenocarcinoma of the lung. Proc Natl Acad Sci USA 2001; 98(24): 13784–13789

    Article  PubMed  CAS  Google Scholar 

  15. Bhattacharjee A, Richards WG, Staunton J, Li C, Monti S, Vasa P, Ladd C, Beheshti J, Bueno R, Gillette M, Loda M, Weber G, Mark EJ, Lander ES, Wong W, Johnson BE, Golub TR, Sugarbaker DJ, Meyerson M. Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. Proc Natl Acad Sci USA 2001; 98(24): 13790–13795

    Article  PubMed  CAS  Google Scholar 

  16. Hosseinzadeh F, Ebrahimi M, Goliaei B, Shamabadi N. Classification of lung cancer tumors based on structural and physicochemical properties of proteins by bioinformatics models. PLoS ONE 2012; 7(7): e40017

    Article  PubMed  CAS  Google Scholar 

  17. Coello MC, Luketich JD, Litle VR, Godfrey TE. Prognostic significance of micrometastasis in non-small-cell lung cancer. Clin Lung Cancer 2004; 5(4): 214–225

    Article  PubMed  Google Scholar 

  18. Xi L, Lyons-Weiler J, Coello MC, Huang X, Gooding WE, Luketich JD, Godfrey TE. Prediction of lymph node metastasis by analysis of gene expression profiles in primary lung adenocarcinomas. Clin Cancer Res 2005; 11(11): 4128–4135

    Article  PubMed  CAS  Google Scholar 

  19. Beer DG, Kardia SL, Huang CC, Giordano TJ, Levin AM, Misek DE, Lin L, Chen G, Gharib TG, Thomas DG, Lizyness ML, Kuick R, Hayasaka S, Taylor JM, Iannettoni MD, Orringer MB, Hanash S. Gene-expression profiles predict survival of patients with lung adenocarcinoma. Nat Med 2002; 8(8): 816–824

    PubMed  CAS  Google Scholar 

  20. Takada M, Tada M, Tamoto E, Kawakami A, Murakawa K, Shindoh G, Teramoto K, Matsunaga A, Komuro K, Kanai M, Fujiwara Y, Shirata K, Nishimura N, Miyamoto M, Okushiba S, Kondo S, Hamada J, Katoh H, Yoshiki T, Moriuchi T. Prediction of lymph node metastasis by analysis of gene expression profiles in non-small cell lung cancer. J Surg Res 2004; 122(1): 61–69

    Article  PubMed  CAS  Google Scholar 

  21. Wu K, House L, Liu W, Cho WC. Personalized targeted therapy for lung cancer. Int J Mol Sci 2012; 13(9): 11471–11496

    Article  PubMed  CAS  Google Scholar 

  22. Bozic I, Antal T, Ohtsuki H, Carter H, Kim D, Chen S, Karchin R, Kinzler KW, Vogelstein B, Nowak MA. Accumulation of driver and passenger mutations during tumor progression. Proc Natl Acad Sci USA 2010; 107(43): 18545–18550

    Article  PubMed  CAS  Google Scholar 

  23. M. G. Kris BEJ. D. J. Kwiatkowski. Identification of driver mutations in tumor specimens from 1,000 patients with lung adenocarcinoma: The NCI’s Lung Cancer Mutation Consortium (LCMC). Journal of Clinical Oncology, 2011 ASCO Annual Meeting Proceedings (Post-Meeting Edition) 2011; 29(18): CRA7506

    Google Scholar 

  24. Ausborn NL, Le QT, Bradley JD, Choy H, Dicker AP, Saha D, Simko J, Story MD, Torossian A, Lu B. Molecular profiling to optimize treatment in non-small cell lung cancer: a review of potential molecular targets for radiation therapy by the translational research program of the radiation therapy oncology group. Int J Radiat Oncol Biol Phys 2012; 83(4): e453–e464

    Article  PubMed  CAS  Google Scholar 

  25. Shaw AT, Yeap BY, Mino-Kenudson M, Digumarthy SR, Costa DB, Heist RS, Solomon B, Stubbs H, Admane S, McDermott U, Settleman J, Kobayashi S, Mark EJ, Rodig SJ, Chirieac LR, Kwak EL, Lynch TJ, Iafrate AJ. Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J Clin Oncol 2009; 27(26): 4247–4253

    Article  PubMed  CAS  Google Scholar 

  26. Paik PK, Arcila ME, Fara M, Sima CS, Miller VA, Kris MG, Ladanyi M, Riely GJ. Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. J Clin Oncol 2011; 29(15): 2046–2051

    Article  PubMed  Google Scholar 

  27. West L, Vidwans SJ, Campbell NP, Shrager J, Simon GR, Bueno R, Dennis PA, Otterson GA, Salgia R. A novel classification of lung cancer into molecular subtypes. PLoS ONE 2012; 7(2): e31906

    Article  PubMed  CAS  Google Scholar 

  28. Yamauchi M, Yamaguchi R, Nakata A, Kohno T, Nagasaki M, Shimamura T, Imoto S, Saito A, Ueno K, Hatanaka Y, Yoshida R, Higuchi T, Nomura M, Beer DG, Yokota J, Miyano S, Gotoh N. Epidermal growth factor receptor tyrosine kinase defines critical prognostic genes of stage I lung adenocarcinoma. PLoS ONE 2012; 7(9): e43923

    Article  PubMed  CAS  Google Scholar 

  29. Bunn PA Jr, Doebele RC. Genetic testing for lung cancer: reflex versus clinical selection. J Clin Oncol 2011; 29(15): 1943–1945

    Article  PubMed  Google Scholar 

  30. Wan YW, Sabbagh E, Raese R, Qian Y, Luo D, Denvir J, Vallyathan V, Castranova V, Guo NL. Hybrid models identified a 12-gene signature for lung cancer prognosis and chemoresponse prediction. PLoS ONE 2010; 5(8): e12222

    Article  PubMed  Google Scholar 

  31. Chen DT, Hsu YL, Fulp WJ, Coppola D, Haura EB, Yeatman TJ, Cress WD. Prognostic and predictive value of a malignancy-risk gene signature in early-stage non-small cell lung cancer. J Natl Cancer Inst 2011; 103(24): 1859–1870

    Article  PubMed  CAS  Google Scholar 

  32. Kim ES, Herbst RS, Wistuba II, Lee JJ, Blumenschein GR Jr, Tsao A, Stewart DJ, Hicks ME, Erasmus J Jr, Gupta S, Alden CM, Liu S, Tang X, Khuri FR, Tran HT, Johnson BE, Heymach JV, Mao L, Fossella F, Kies MS, Papadimitrakopoulou V, Davis SE, Lippman SM, Hong WK. The BATTLE trial: personalizing therapy for lung cancer. Cancer Discov 2011; 1(1): 44–53

    Article  PubMed  CAS  Google Scholar 

  33. Hou J, Lambers M, den Hamer B, den Bakker MA, Hoogsteden HC, Grosveld F, Hegmans J, Aerts J, Philipsen S. Expression profilingbased subtyping identifies novel non-small cell lung cancer subgroups and implicates putative resistance to pemetrexed therapy. J Thorac Oncol 2012; 7(1): 105–114

    Article  PubMed  CAS  Google Scholar 

  34. Torres-Roca JF, Eschrich S, Zhao H, Bloom G, Sung J, McCarthy S, Cantor AB, Scuto A, Li C, Zhang S, Jove R, Yeatman T. Prediction of radiation sensitivity using a gene expression classifier. Cancer Res 2005; 65(16): 7169–7176

    Article  PubMed  CAS  Google Scholar 

  35. Eschrich S, Zhang H, Zhao H, Boulware D, Lee JH, Bloom G, Torres-Roca JF. Systems biology modeling of the radiation sensitivity network: a biomarker discovery platform. Int J Radiat Oncol Biol Phys 2009; 75(2): 497–505

    Article  PubMed  CAS  Google Scholar 

  36. Flehinger BJ, Kimmel M, Melamed MR. The effect of surgical treatment on survival from early lung cancer. Implications for screening. Chest 1992; 101(4): 1013–1018

    Article  PubMed  CAS  Google Scholar 

  37. Larsen JE, Pavey SJ, Passmore LH, Bowman RV, Hayward NK, Fong KM. Gene expression signature predicts recurrence in lung adenocarcinoma. Clin Cancer Res 2007; 13(10): 2946–2954

    Article  PubMed  CAS  Google Scholar 

  38. Bild AH, Yao G, Chang JT, Wang Q, Potti A, Chasse D, Joshi MB, Harpole D, Lancaster JM, Berchuck A, Olson JA Jr, Marks JR, Dressman HK, West M, Nevins JR. Oncogenic pathway signatures in human cancers as a guide to targeted therapies. Nature 2006; 439(7074): 353–357

    Article  PubMed  CAS  Google Scholar 

  39. 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(17): 2793–2799

    Article  PubMed  CAS  Google Scholar 

  40. 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(1): e30880

    Article  PubMed  CAS  Google Scholar 

  41. Guo L, Ma Y, Ward R, Castranova V, Shi X, Qian Y. Constructing molecular classifiers for the accurate prognosis of lung adenocarcinoma. Clin Cancer Res 2006; 12(11 Pt 1): 3344–3354

    Article  PubMed  CAS  Google Scholar 

  42. Lu Y, Lemon W, Liu PY, Yi Y, Morrison C, Yang P, Sun Z, Szoke J, Gerald WL, Watson M, Govindan R, You M. A gene expression signature predicts survival of patients with stage I non-small cell lung cancer. PLoS Med 2006; 3(12): e467

    Article  PubMed  Google Scholar 

  43. Endoh H, Tomida S, Yatabe Y, Konishi H, Osada H, Tajima K, Kuwano H, Takahashi T, Mitsudomi T. Prognostic model of pulmonary adenocarcinoma by expression profiling of eight genes as determined by quantitative real-time reverse transcriptase polymerase chain reaction. J Clin Oncol 2004; 22(5): 811–819

    Article  PubMed  CAS  Google Scholar 

  44. Sun Z, Wigle DA, Yang P. Non-overlapping and non-cell-typespecific gene expression signatures predict lung cancer survival. J Clin Oncol 2008; 26(6): 877–883

    Article  PubMed  Google Scholar 

  45. Raponi M, Zhang Y, Yu J, Chen G, Lee G, Taylor JM, Macdonald J, Thomas D, Moskaluk C, Wang Y, Beer DG. Gene expression signatures for predicting prognosis of squamous cell and adenocarcinomas of the lung. Cancer Res 2006; 66(15): 7466–7472

    Article  PubMed  CAS  Google Scholar 

  46. Roepman P, Jassem J, Smit EF, Muley T, Niklinski J, van de Velde T, Witteveen AT, Rzyman W, Floore A, Burgers S, Giaccone G, Meister M, Dienemann H, Skrzypski M, Kozlowski M, Mooi WJ, van Zandwijk N. An immune response enriched 72-gene prognostic profile for early-stage non-small-cell lung cancer. Clin Cancer Res 2009; 15(1): 284–290

    Article  PubMed  CAS  Google Scholar 

  47. Seike M, Yanaihara N, Bowman ED, Zanetti KA, Budhu A, Kumamoto K, Mechanic LE, Matsumoto S, Yokota J, Shibata T, Sugimura H, Gemma A, Kudoh S, Wang XW, Harris CC. Use of a cytokine gene expression signature in lung adenocarcinoma and the surrounding tissue as a prognostic classifier. J Natl Cancer Inst 2007; 99(16): 1257–1269

    Article  PubMed  CAS  Google Scholar 

  48. Lu Y, Govindan R, Wang L, Liu PY, Goodgame B, Wen W, Sezhiyan A, Pfeifer J, Li YF, Hua X, Wang Y, Yang P, You M. MicroRNA profiling and prediction of recurrence/relapse-free survival in stage I lung cancer. Carcinogenesis 2012; 33(5): 1046–1054

    Article  PubMed  CAS  Google Scholar 

  49. Lau SK, Boutros PC, Pintilie M, Blackhall FH, Zhu CQ, Strumpf D, Johnston MR, Darling G, Keshavjee S, Waddell TK, Liu N, Lau D, Penn LZ, Shepherd FA, Jurisica I, Der SD, Tsao MS. Three-gene prognostic classifier for early-stage non small-cell lung cancer. J Clin Oncol 2007; 25(35): 5562–5569

    Article  PubMed  Google Scholar 

  50. Chen HY, Yu SL, Chen CH, Chang GC, Chen CY, Yuan A, Cheng CL, Wang CH, Terng HJ, Kao SF, Chan WK, Li HN, Liu CC, Singh S, Chen WJ, Chen JJ, Yang PC. A five-gene signature and clinical outcome in non-small-cell lung cancer. N Engl J Med 2007; 356(1): 11–20

    Article  PubMed  CAS  Google Scholar 

  51. Okayama H, Kohno T, Ishii Y, Shimada Y, Shiraishi K, Iwakawa R, Furuta K, Tsuta K, Shibata T, Yamamoto S, Watanabe S, Sakamoto H, Kumamoto K, Takenoshita S, Gotoh N, Mizuno H, Sarai A, Kawano S, Yamaguchi R, Miyano S, Yokota J. Identification of genes upregulated in ALK-positive and EGFR/KRAS/ALKnegative lung adenocarcinomas. Cancer Res 2012; 72(1): 100–111

    Article  PubMed  CAS  Google Scholar 

  52. Xie Y, Xiao G, Coombes KR, Behrens C, Solis LM, Raso G, Girard L, Erickson HS, Roth J, Heymach JV, Moran C, Danenberg K, Minna JD, Wistuba II. Robust gene expression signature from formalin-fixed paraffin-embedded samples predicts prognosis of non-small-cell lung cancer patients. Clin Cancer Res 2011; 17(17): 5705–5714

    Article  PubMed  CAS  Google Scholar 

  53. Shedden K, Taylor JM, Enkemann SA, Tsao MS, Yeatman TJ, Gerald WL, Eschrich S, Jurisica I, Giordano TJ, Misek DE, Chang AC, Zhu CQ, Strumpf D, Hanash S, Shepherd FA, Ding K, Seymour L, Naoki K, Pennell N, Weir B, Verhaak R, Ladd-Acosta C, Golub T, Gruidl M, Sharma A, Szoke J, Zakowski M, Rusch V, Kris M, Viale A, Motoi N, Travis W, Conley B, Seshan VE, Meyerson M, Kuick R, Dobbin KK, Lively T, Jacobson JW, Beer DG, Shedden K, Taylor JMG, Enkemann SA, Tsao MS, Yeatman TJ, Gerald WL, Eschrich S, Jurisica I, Giordano TJ, Misek DE, Chang AC, Zhu CQ, Strumpf D, Hanash S, Shepherd FA, Ding K, Seymour L, Naoki K, Pennell N, Weir B, Verhaak R, Ladd-Acosta C, Golub T, Gruidl M, Sharma A, Szoke J, Zakowski M, Rusch V, Kris M, Viale A, Motoi N, Travis W, Conley B, Seshan VE, Meyerson M, Kuick R, Dobbin KK, Lively T, Jacobson JW, Beer DG. Gene expression-based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study. Nat Med 2008; 14(8): 822–827

    Article  PubMed  CAS  Google Scholar 

  54. Song D, Zhukov TA, Markov O, Qian W, Tockman MS. A new method for lung cancer prognosis via centrosome image feature analysis. Anal Quant Cytol Histol 2012; 34(4): 180–188

    PubMed  Google Scholar 

  55. Sharma S, Kelly TK, Jones PA. Epigenetics in cancer. Carcinogenesis 2010; 31(1): 27–36

    Article  PubMed  CAS  Google Scholar 

  56. You JS, Jones PA. Cancer genetics and epigenetics: two sides of the same coin? Cancer Cell 2012; 22(1): 9–20

    Article  PubMed  CAS  Google Scholar 

  57. Belinsky SA. Gene-promoter hypermethylation as a biomarker in lung cancer. Nat Rev Cancer 2004; 4(9): 707–717

    Article  PubMed  CAS  Google Scholar 

  58. Shinjo K, Okamoto Y, An B, Yokoyama T, Takeuchi I, Fujii M, Osada H, Usami N, Hasegawa Y, Ito H, Hida T, Fujimoto N, Kishimoto T, Sekido Y, Kondo Y. Integrated analysis of genetic and epigenetic alterations reveals CpG island methylator phenotype associated with distinct clinical characters of lung adenocarcinoma. Carcinogenesis 2012; 33(7): 1277–1285

    Article  PubMed  CAS  Google Scholar 

  59. Ehrich M, Field JK, Liloglou T, Xinarianos G, Oeth P, Nelson MR, Cantor CR, van den Boom D. Cytosine methylation profiles as a molecular marker in non-small cell lung cancer. Cancer Res 2006; 66(22): 10911–10918

    Article  PubMed  CAS  Google Scholar 

  60. Baffa R, Fassan M, Volinia S, O’Hara B, Liu CG, Palazzo JP, Gardiman M, Rugge M, Gomella LG, Croce CM, Rosenberg A. MicroRNA expression profiling of human metastatic cancers identifies cancer gene targets. J Pathol 2009; 219(2): 214–221

    Article  PubMed  CAS  Google Scholar 

  61. Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, Stephens RM, Okamoto A, Yokota J, Tanaka T, Calin GA, Liu CG, Croce CM, Harris CC. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 2006; 9(3): 189–198

    Article  PubMed  CAS  Google Scholar 

  62. Rosenfeld N, Aharonov R, Meiri E, Rosenwald S, Spector Y, Zepeniuk M, Benjamin H, Shabes N, Tabak S, Levy A, Lebanony D, Goren Y, Silberschein E, Targan N, Ben-Ari A, Gilad S, Sion-Vardy N, Tobar A, Feinmesser M, Kharenko O, Nativ O, Nass D, Perelman M, Yosepovich A, Shalmon B, Polak-Charcon S, Fridman E, Avniel A, Bentwich I, Bentwich Z, Cohen D, Chajut A, Barshack I. MicroRNAs accurately identify cancer tissue origin. Nat Biotechnol 2008; 26(4): 462–469

    Article  PubMed  CAS  Google Scholar 

  63. Landi MT, Zhao Y, Rotunno M, Koshiol J, Liu H, Bergen AW, Rubagotti M, Goldstein AM, Linnoila I, Marincola FM, Tucker MA, Bertazzi PA, Pesatori AC, Caporaso NE, McShane LM, Wang E. MicroRNA expression differentiates histology and predicts survival of lung cancer. Clin Cancer Res 2010; 16(2): 430–441

    Article  PubMed  CAS  Google Scholar 

  64. Tan X, Qin W, Zhang L, Hang J, Li B, Zhang C, Wan J, Zhou F, Shao K, Sun Y, Wu J, Zhang X, Qiu B, Li N, Shi S, Feng X, Zhao S, Wang Z, Zhao X, Chen Z, Mitchelson K, Cheng J, Guo Y, He J. A 5-microRNA signature for lung squamous cell carcinoma diagnosis and hsa-miR-31 for prognosis. Clin Cancer Res 2011; 17(21): 6802–6811

    Article  PubMed  CAS  Google Scholar 

  65. Bishop JA, Benjamin H, Cholakh H, Chajut A, Clark DP, Westra WH. Accurate classification of non-small cell lung carcinoma using a novel microRNA-based approach. Clin Cancer Res 2010; 16(2): 610–619

    Article  PubMed  CAS  Google Scholar 

  66. Del Vescovo V, Cantaloni C, Cucino A, Girlando S, Silvestri M, Bragantini E, Fasanella S, Cuorvo LV, Palma PD, Rossi G, Papotti M, Pelosi G, Graziano P, Cavazza A, Denti MA, Barbareschi M. miR-205 Expression levels in nonsmall cell lung cancer do not always distinguish adenocarcinomas from squamous cell carcinomas. Am J Surg Pathol 2011; 35(2): 268–275

    Article  PubMed  Google Scholar 

  67. Kikuchi T, Carbone DP. Proteomics analysis in lung cancer: challenges and opportunities. Respirology 2007; 12(1): 22–28

    Article  PubMed  Google Scholar 

  68. Tacha D, Yu C, Bremer R, Qi W, Haas T. A 6-antibody panel for the classification of lung adenocarcinoma versus squamous cell carcinoma. Appl Immunohistochem Mol Morphol 2012; 20(3): 201–207

    Article  PubMed  CAS  Google Scholar 

  69. Anagnostou VK, Dimou AT, Botsis T, Killiam EJ, Gustavson MD, Homer RJ, Boffa D, Zolota V, Dougenis D, Tanoue L, Gettinger SN, Detterbeck FC, Syrigos KN, Bepler G, Rimm DL. Molecular classification of nonsmall cell lung cancer using a 4-protein quantitative assay. Cancer 2012; 118(6): 1607–1618

    Article  PubMed  CAS  Google Scholar 

  70. Janssen-Heijnen ML, Coebergh JW. The changing epidemiology of lung cancer in Europe. Lung Cancer 2003; 41(3): 245–258

    Article  PubMed  Google Scholar 

  71. Perez-Moreno P, Brambilla E, Thomas R, Soria JC. Squamous cell carcinoma of the lung: molecular subtypes and therapeutic opportunities. Clin Cancer Res 2012; 18(9): 2443–2451

    Article  PubMed  CAS  Google Scholar 

  72. Hammerman PS, Hayes DN, Wilkerson MD, Schultz N, Bose R, Chu A, Collisson EA, Cope L, Creighton CJ, Getz G, Herman JG, Johnson BE, Kucherlapati R, Ladanyi M, Maher CA, Robertson G, Sander C, Shen R, Sinha R, Sivachenko A, Thomas RK, Travis WD, Tsao MS, Weinstein JN, Wigle DA, Baylin SB, Govindan R, Meyerson M. Comprehensive genomic characterization of squamous cell lung cancers. Nature 2012; 489(7417): 519–525

    Article  CAS  Google Scholar 

  73. Hammerman PS, Sos ML, Ramos AH, Xu C, Dutt A, Zhou W, Brace LE, Woods BA, Lin W, Zhang J, Deng X, Lim SM, Heynck S, Peifer M, Simard JR, Lawrence MS, Onofrio RC, Salvesen HB, Seidel D, Zander T, Heuckmann JM, Soltermann A, Moch H, Koker M, Leenders F, Gabler F, Querings S, Ansén S, Brambilla E, Brambilla C, Lorimier P, Brustugun OT, Helland A, Petersen I, Clement JH, Groen H, Timens W, Sietsma H, Stoelben E, Wolf J, Beer DG, Tsao MS, Hanna M, Hatton C, Eck MJ, Janne PA, Johnson BE, Winckler W, Greulich H, Bass AJ, Cho J, Rauh D, Gray NS, Wong KK, Haura EB, Thomas RK, Meyerson M. Mutations in the DDR2 kinase gene identify a novel therapeutic target in squamous cell lung cancer. Cancer Discov 2011; 1(1): 78–89

    Article  PubMed  CAS  Google Scholar 

  74. Weiss J, Sos ML, Seidel D, Peifer M, Zander T, Heuckmann JM, Ullrich RT, Menon R, Maier S, Soltermann A, Moch H, Wagener P, Fischer F, Heynck S, Koker M, Schöttle J, Leenders F, Gabler F, Dabow I, Querings S, Heukamp LC, Balke-Want H, Ansén S, Rauh D, Baessmann I, Altmüller J, Wainer Z, Conron M, Wright G, Russell P, Solomon B, Brambilla E, Brambilla C, Lorimier P, Sollberg S, Brustugun OT, Engel-Riedel W, Ludwig C, Petersen I, Sänger J, Clement J, Groen H, Timens W, Sietsma H, Thunnissen E, Smit E, Heideman D, Cappuzzo F, Ligorio C, Damiani S, Hallek M, Beroukhim R, Pao W, Klebl B, Baumann M, Buettner R, Ernestus K, Stoelben E, Wolf J, Nürnberg P, Perner S, Thomas RK. Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer. Sci Transl Med 2010; 2(62): 62ra93

    Article  PubMed  CAS  Google Scholar 

  75. Belvedere O, Berri S, Chalkley R, Conway C, Barbone F, Pisa F, MacLennan K, Daly C, Alsop M, Morgan J, Menis J, Tcherveniakov P, Papagiannopoulos K, Rabbitts P, Wood HM. A computational index derived from whole-genome copy number analysis is a novel tool for prognosis in early stage lung squamous cell carcinoma. Genomics 2012; 99(1): 18–24

    Article  PubMed  CAS  Google Scholar 

  76. Imielinski M, Berger AH, Hammerman PS, Hernandez B, Pugh TJ, Hodis E, Cho J, Suh J, Capelletti M, Sivachenko A, Sougnez C, Auclair D, Lawrence MS, Stojanov P, Cibulskis K, Choi K, deWaal L, Sharifnia T, Brooks A, Greulich H, Banerji S, Zander T, Seidel D, Leenders F, Ansén S, Ludwig C, Engel-Riedel W, Stoelben E, Wolf J, Goparju C, Thompson K, Winckler W, Kwiatkowski D, Johnson BE, Jänne PA, Miller VA, Pao W, Travis WD, Pass HI, Gabriel SB, Lander ES, Thomas RK, Garraway LA, Getz G, Meyerson M. Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell 2012; 150(6): 1107–1120

    Article  PubMed  CAS  Google Scholar 

  77. Seo JS, Ju YS, Lee WC, Shin JY, Lee JK, Bleazard T, Lee J, Jung YJ, Kim JO, Shin JY, Yu SB, Kim J, Lee ER, Kang CH, Park IK, Rhee H, Lee SH, Kim JI, Kang JH, Kim YT. The transcriptional landscape and mutational profile of lung adenocarcinoma. Genome Res 2012; 22(11): 2109–2119

    Article  PubMed  CAS  Google Scholar 

  78. Lipson D, Capelletti M, Yelensky R, Otto G, Parker A, Jarosz M, Curran JA, Balasubramanian S, Bloom T, Brennan KW, Donahue A, Downing SR, Frampton GM, Garcia L, Juhn F, Mitchell KC, White E, White J, Zwirko Z, Peretz T, Nechushtan H, Soussan-Gutman L, Kim J, Sasaki H, Kim HR, Park SI, Ercan D, Sheehan CE, Ross JS, Cronin MT, Jänne PA, Stephens PJ. Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nat Med 2012; 18(3): 382–384

    Article  PubMed  CAS  Google Scholar 

  79. Ju YS, Lee WC, Shin JY, Lee S, Bleazard T, Won JK, Kim YT, Kim JI, Kang JH, Seo JS. A transforming KIF5B and RET gene fusion in lung adenocarcinoma revealed from whole-genome and transcriptome sequencing. Genome Res 2012; 22(3): 436–445

    Article  PubMed  CAS  Google Scholar 

  80. Kohno T, Ichikawa H, Totoki Y, Yasuda K, Hiramoto M, Nammo T, Sakamoto H, Tsuta K, Furuta K, Shimada Y, Iwakawa R, Ogiwara H, Oike T, Enari M, Schetter AJ, Okayama H, Haugen A, Skaug V, Chiku S, Yamanaka I, Arai Y, Watanabe S, Sekine I, Ogawa S, Harris CC, Tsuda H, Yoshida T, Yokota J, Shibata T. KIF5B-RET fusions in lung adenocarcinoma. Nat Med 2012; 18(3): 375–377

    Article  PubMed  CAS  Google Scholar 

  81. Govindan R, Ding L, Griffith M, Subramanian J, Dees ND, Kanchi KL, Maher CA, Fulton R, Fulton L, Wallis J, Chen K, Walker J, McDonald S, Bose R, Ornitz D, Xiong D, You M, Dooling DJ, Watson M, Mardis ER, Wilson RK. Genomic landscape of nonsmall cell lung cancer in smokers and never-smokers. Cell 2012; 150(6): 1121–1134

    Article  PubMed  CAS  Google Scholar 

  82. Mardis ER. Anticipating the 1,000 dollar genome. Genome Biol 2006; 7(7): 112

    Article  PubMed  Google Scholar 

  83. Mardis ER. The $ 1,000 genome, the $100,000 analysis? Genome Med 2010; 2(11): 84

    Article  PubMed  Google Scholar 

  84. Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, Fujiwara S, Watanabe H, Kurashina K, Hatanaka H, Bando M, Ohno S, Ishikawa Y, Aburatani H, Niki T, Sohara Y, Sugiyama Y, Mano H. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 2007; 448(7153): 561–566

    Article  PubMed  CAS  Google Scholar 

  85. Bang YJ. Treatment of ALK-positive non-small cell lung cancer. Arch Pathol Lab Med 2012; 136(10): 1201–1204

    Article  PubMed  CAS  Google Scholar 

  86. Chin L, Andersen JN, Futreal PA. Cancer genomics: from discovery science to personalized medicine. Nat Med 2011; 17(3): 297–303

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Thoracic Surgery, Cancer Institute and Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100021, China

    Yue Yu & Jie He

Authors
  1. Yue Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jie He
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jie He.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yu, Y., He, J. Molecular classification of non-small-cell lung cancer: diagnosis, individualized treatment, and prognosis. Front. Med. 7, 157–171 (2013). https://doi.org/10.1007/s11684-013-0272-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11684-013-0272-4

Keywords

Search

Navigation