Molecular Diagnosis & Therapy

, Volume 16, Issue 1, pp 1–6 | Cite as

Molecular Signatures of Lung Cancer

Defining New Diagnostic and Therapeutic Paradigms
Current Opinion


Molecular profiling holds great promise for improving our ability to diagnose, prognosticate, and select individualized treatments for lung cancer patients. However, using multidimensional data and novel technologies to derive these profiles is limited by our ability to employ the assay in a clinical scenario where it can impact the course of disease. Although many molecular signatures have been reported in lung cancer, as of yet, few have been sufficiently validated for widespread clinical use. Recently, several novel signatures have been reported, which address critical aspects of patient care and/or demonstrate improved efforts for appropriate clinical validation. Here, we present our opinion on the current state of the field of molecular signatures in lung cancer.



J.M.B. is a cofounder, vice president, and shareholder of TrackFive Diagnostics, Inc. C.L.A. has no conflicts of interest that are directly relevant to the content of this article.


  1. 1.
    Siegel R, Ward E, Brawley O, et al. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 2011 Jul–Aug; 61(4): 212–36PubMedCrossRefGoogle Scholar
  2. 2.
    Subramanian J, Simon R. Gene expression-based prognostic signatures in lung cancer: ready for clinical use? J Natl Cancer Inst 2010 Apr 7; 102(7): 464–74PubMedCrossRefGoogle Scholar
  3. 3.
    Carrola J, Rocha CM, Barros AS, et al. Metabolic signatures of lung cancer in biofluids: NMR-based metabonomics of urine. J Proteome Res 2011 Jan 7; 10(1): 221–30PubMedCrossRefGoogle Scholar
  4. 4.
    Rocha CM, Barros AS, Gil AM, et al. Metabolic profiling of human lung cancer tissue by 1H high resolution magic angle spinning (HRMAS) NMR spectroscopy. J Proteome Res 2010 Jan; 9(1): 319–32PubMedCrossRefGoogle Scholar
  5. 5.
    Rocha CM, Carrola J, Barros AS, et al. Metabolic signatures of lung cancer in biofluids: NMR-based metabonomics of blood plasma. J Proteome Res 2011 Aug 5; 10(9): 4314–24PubMedCrossRefGoogle Scholar
  6. 6.
    Beer DG, Kardia SL, Huang CC, et al. Gene-expression profiles predict survival of patients with lung adenocarcinoma. Nat Med 2002 Aug; 8(8): 816–24PubMedGoogle Scholar
  7. 7.
    Boutros PC, Lau SK, Pintilie M, et al. Prognostic gene signatures for non-small-cell lung cancer. Proc Natl Acad Sci U S A 2009 Feb 24; 106(8): 2824–8PubMedCrossRefGoogle Scholar
  8. 8.
    Chen HY, Yu SL, Chen CH, et al. A five-gene signature and clinical outcome in non-small-cell lung cancer. N Engl J Med 2007 Jan 4; 356 (1): 11–20Google Scholar
  9. 9.
    Guo L, Ma Y, Ward R, et al. Constructing molecular classifiers for the accurate prognosis of lung adenocarcinoma. Clin Cancer Res 2006 Jun 1; 12 (11 Pt 1): 3344–54PubMedCrossRefGoogle Scholar
  10. 10.
    Kadara H, Behrens C, Yuan P, et al. A five-gene and corresponding protein signature for stage-I lung adenocarcinoma prognosis. Clin Cancer Res 2011 Mar 15; 17(6): 1490–501PubMedCrossRefGoogle Scholar
  11. 11.
    Larsen JE, Pavey SJ, Passmore LH, et al. Expression profiling defines a recurrence signature in lung squamous cell carcinoma. Carcinogenesis 2007 Mar; 28(3): 760–6PubMedCrossRefGoogle Scholar
  12. 12.
    Larsen JE, Pavey SJ, Passmore LH, et al. Gene expression signature predicts recurrence in lung adenocarcinoma. Clin Cancer Res 2007 May 15; 13(10): 2946–54PubMedCrossRefGoogle Scholar
  13. 13.
    Lau SK, Boutros PC, Pintilie M, et al. Three-gene prognostic classifier for early-stage non small-cell lung cancer. J Clin Oncol 2007 Dec 10; 25(35): 5562–9PubMedCrossRefGoogle Scholar
  14. 14.
    Lu Y, Lemon W, Liu PY, et al. A gene expression signature predicts survival of patients with stage I non-small cell lung cancer. PLoS Med 2006 Dec; 3(12): e467PubMedCrossRefGoogle Scholar
  15. 15.
    Raponi M, Zhang Y, Yu J, et al. Gene expression signatures for predicting prognosis of squamous cell and adenocarcinomas of the lung. Cancer Res 2006 Aug 1; 66(15): 7466–72PubMedCrossRefGoogle Scholar
  16. 16.
    Raz DJ, Ray MR, Kim JY, et al. A multigene assay is prognostic of survival in patients with early-stage lung adenocarcinoma. Clin Cancer Res 2008 Sep 1; 14(17): 5565–70PubMedCrossRefGoogle Scholar
  17. 17.
    Roepman P, Jassem J, Smit EF, et al. An immune response enriched 72-gene prognostic profile for early-stage non-small-cell lung cancer. Clin Cancer Res 2009 Jan 1; 15(1): 284–90PubMedCrossRefGoogle Scholar
  18. 18.
    Shedden K, Taylor JM, Enkemann SA, et al. Gene expression-based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study. Nat Med 2008 Aug; 14(8): 822–7PubMedCrossRefGoogle Scholar
  19. 19.
    Skrzypski M, Jassem E, Taron M, et al. Three-gene expression signature predicts survival in early-stage squamous cell carcinoma of the lung. Clin Cancer Res 2008 Aug 1; 14(15): 4794–9PubMedCrossRefGoogle Scholar
  20. 20.
    Sun Z, Wigle DA, Yang P. Non-overlapping and non-cell-type-specific gene expression signatures predict lung cancer survival. J Clin Oncol 2008 Feb 20; 26(6): 877–83PubMedCrossRefGoogle Scholar
  21. 21.
    Tomida S, Koshikawa K, Yatabe Y, et al. Gene expression-based, individualized outcome prediction for surgically treated lung cancer patients. Oncogene 2004 Jul 8; 23(31): 5360–70PubMedCrossRefGoogle Scholar
  22. 22.
    Zhu CQ, Ding K, Strumpf D, et al. Prognostic and predictive gene signature for adjuvant chemotherapy in resected non-small-cell lung cancer. J Clin Oncol 2010 Oct 10; 28(29): 4417–24PubMedCrossRefGoogle Scholar
  23. 23.
    Nesbitt JC, Putnam Jr JB, Walsh GL, et al. Survival in early-stage non-small cell lung cancer. Ann Thorac Surg 1995 Aug; 60(2): 466–72PubMedCrossRefGoogle Scholar
  24. 24.
    National Comprehensive Cancer Network. NCCN practice guidelines in oncology: small cell lung cancer [online]. Available from URL: [Accessed 2012 Jan 20]
  25. 25.
    National Comprehensive Cancer Network. NCCN practice guidelines in oncology: non-small cell lung cancer [online]. Available from URL: [Accessed 2012 Jan 20]
  26. 26.
    Winton T, Livingston R, Johnson D, et al. Vinorelbine plus cisplatin vs observation in resected non-small-cell lung cancer. N Engl J Med 2005 Jun 23; 352(25): 2589–97PubMedCrossRefGoogle Scholar
  27. 27.
    Arriagada R, Bergman B, Dunant A, et al. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med 2004 Jan 22; 350(4): 351–60PubMedCrossRefGoogle Scholar
  28. 28.
    Pignon JP, Tribodet H, Scagliotti GV, et al. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol 2008 Jul 20; 26(21): 3552–9PubMedCrossRefGoogle Scholar
  29. 29.
    Kratz JR, Jablons DM. Genomic prognostic models in early-stage lung cancer. Clin Lung Cancer 2009 May; 10(3): 151–7PubMedCrossRefGoogle Scholar
  30. 30.
    Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 2004 Dec 30; 351(27): 2817–26PubMedCrossRefGoogle Scholar
  31. 31.
    Keller A, Leidinger P, Gislefoss R, et al. Stable serum miRNA profiles as potential tool for non-invasive lung cancer diagnosis. RNA Biol 2011 May 1; 8(3): 506–16PubMedCrossRefGoogle Scholar
  32. 32.
    Bianchi F, Nicassio F, Marzi M, et al. A serum circulating miRNA diagnostic test to identify asymptomatic high-risk individuals with early stage lung cancer. EMBO Mol Med 2011 Aug; 3(8): 495–503PubMedCrossRefGoogle Scholar
  33. 33.
    Azuma K, Okamoto I, Kawahara A, et al. Association of the expression of mutant epidermal growth factor receptor protein as determined with mutation-specific antibodies in non-small cell lung cancer with progression-free survival after gefitinib treatment. J Thorac Oncol 2012 Jan; 7(1): 122–7PubMedCrossRefGoogle Scholar
  34. 34.
    Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010 Jun 24; 362(25): 2380–8PubMedCrossRefGoogle Scholar
  35. 35.
    Kim DW, Lee SH, Lee JS, et al. A multicenter phase II study to evaluate the efficacy and safety of gefitinib as first-line treatment for Korean patients with advanced pulmonary adenocarcinoma harboring EGFR mutations. Lung Cancer 2011 Jan; 71(1): 65–9PubMedCrossRefGoogle Scholar
  36. 36.
    Douillard JY, Shepherd FA, Hirsh V, et al. Molecular predictors of outcome with gefitinib and docetaxel in previously treated non-small-cell lung cancer: data from the randomized phase III INTEREST trial. J Clin Oncol 2010 Feb 10; 28(5): 744–52PubMedCrossRefGoogle Scholar
  37. 37.
    Rosell R, Moran T, Queralt C, et al. Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med 2009 Sep 3; 361(10): 958–67PubMedCrossRefGoogle Scholar
  38. 38.
    Balko JM, Potti A, Saunders C, et al. Gene expression patterns that predict sensitivity to epidermal growth factor receptor tyrosine kinase inhibitors in lung cancer cell lines and human lung tumors. BMC Genomics 2006; 7: 289PubMedCrossRefGoogle Scholar
  39. 39.
    Coldren CD, Helfrich BA, Witta SE, et al. Baseline gene expression predicts sensitivity to gefitinib in non-small cell lung cancer cell lines. Mol Cancer Res 2006 Aug; 4(8): 521–8PubMedCrossRefGoogle Scholar
  40. 40.
    Balko JM, Black EP. A gene expression predictor of response to EGFR-targeted therapy stratifies progression-free survival to cetuximab in KRAS wild-type metastatic colorectal cancer. BMC Cancer 2009; 9: 145PubMedCrossRefGoogle Scholar
  41. 41.
    Taguchi F, Solomon B, Gregorc V, et al. Mass spectrometry to classify non-small-cell lung cancer patients for clinical outcome after treatment with epidermal growth factor receptor tyrosine kinase inhibitors: a multicohort cross-institutional study. J Natl Cancer Inst 2007 Jun 6; 99(11): 838–46PubMedCrossRefGoogle Scholar
  42. 42.
    Amann JM, Lee JW, Roder H, et al. Genetic and proteomic features associated with survival after treatment with erlotinib in first-line therapy of non-small cell lung cancer in Eastern Cooperative Oncology Group 3503. J Thorac Oncol 2010 Feb; 5(2): 169–78PubMedCrossRefGoogle Scholar
  43. 43.
    Jordheim LP, Seve P, Tredan O, et al. The ribonucleotide reductase large subunit (RRM1) as a predictive factor in patients with cancer. Lancet Oncol 2011 Jul; 12(7): 693–702PubMedCrossRefGoogle Scholar
  44. 44.
    Olaussen KA, Dunant A, Fouret P, et al. DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med 2006 Sep 7; 355(10): 983–91PubMedCrossRefGoogle Scholar
  45. 45.
    Simon GR, Schell MJ, Begum M, et al. Preliminary indication of survival benefit from ERCC1 and RRM1-tailored chemotherapy in patients with advanced nonsmall cell lung cancer: evidence from an individual patient analysis. Cancer. Epub 2011 Oct 25Google Scholar
  46. 46.
    Potti A, Dressman HK, Bild A, et al. Retraction: genomic signatures to guide the use of chemotherapeutics. Nat Med 2011 Jan; 17(1): 135PubMedCrossRefGoogle Scholar
  47. 47.
    Potti A, Mukherjee S, Petersen R, et al. Retraction: a genomic strategy to refine prognosis in early-stage non-small-cell lung cancer. N Engl J Med 2011 Mar 24; 364(12): 1176PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2012

Authors and Affiliations

  1. 1.Department of Medicine, Vanderbilt-Ingram Comprehensive Cancer CenterVanderbilt UniversityNashvilleUSA
  2. 2.Department of Cancer Biology, Vanderbilt-Ingram Comprehensive Cancer CenterVanderbilt UniversityNashvilleUSA
  3. 3.Breast Cancer Research Program, Vanderbilt-Ingram Comprehensive Cancer CenterVanderbilt UniversityNashvilleUSA

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