Central European Journal of Medicine

, Volume 9, Issue 3, pp 382–390 | Cite as

The role of genetic and other biomarkers in NSCLC prognosis

  • Diana Schveigert
  • Saulius Cicenas
  • Jaroslav Bublevic
  • Renatas Askinis
  • Virginijus Sapoka
  • Janina Didziapetriene
Mini-Review
  • 62 Downloads

Abstract

The development of non-small-cell lung cancer (NSCLC) is a multistep process, which is triggered and maintained by various factors. Many steps of non-small-cell lung carcinogenesis, risk factors and biomarkers have been identified; however no consistent model has been established of personalized medicine for these patients. Distinct various gene expression, products of mutated genes and other markers such as circulating nucleic acids or tumor cells has been proven to be potential biomarkers of non-small cell lung cancer as well as potential targets for new treatment strategies. This article will highlight promising biomarkers in non-small cell lung cancer prognosis.

Keywords

Non-small cell lung cancer Biomarkers Prognosis 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. [1]
    Steels E, Paesmans M, Berghmans T, Branle F, Lemaitre F, Mascaux C, Meert AP, Vallot F, Lafitte JJ, Sculier JP. 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(4):705–719PubMedCrossRefGoogle Scholar
  2. [2]
    Gasco A, Molina-Vila MA, Bertran-Alamillo J, Mayo C, Costa C, Capitan AG, Massuti B, Camps C, et al. Association of p53 mutations with progression-free survival (PFS) and overall survival (OS) in EGFR-mutated non-small cell lung cancer (NSCLC) patients (p) treated with erlotinib. J Clin Oncol (Meeting Abstracts) 2012, 30(15):e18143Google Scholar
  3. [3]
    Liu L, Wu C, Wanf Y, Zhong R, Duan S, Wei S, Lin S, Zhang X, Tan W, Yu D, Nie S, Miao X, Lin D. Combined effect of genetic polymorphisms in P53, P73, and MDM2 on non-small cell lung cancer survival. J Thorac Oncol. 2011, 6(11):1793–1800PubMedCrossRefGoogle Scholar
  4. [4]
    Heist RS, Zhou W, Chirieac LR, Cogan-Drew T, Liu G, Su L, Neuberg D, Lynch TJ, Wain JC, Christiani DC. MDM2 polymorphism, survival, and histology in early-stage non-small-cell lung cancer. J Clin Oncol. 2007, 25(16):2243–2247PubMedCrossRefGoogle Scholar
  5. [5]
    Pine SR, Mechanic LE, Bowman ED, Welsh JA. MDM2 SNP309 and SNP354 Are Not Associated with Lung Cancer Risk. Cancer Epidemiol Biomarkers Prev. 2006, 15(8):1559–1561PubMedCrossRefGoogle Scholar
  6. [6]
    Zhuo W, Zhang L, Zhu B, Ling J, Chen Z. Association of MDM2 SNP309 variation with lung cancer risk: evidence from 7196 cases and 8456 controls. PLoS One. 2012, 7(7):e41546PubMedCentralPubMedCrossRefGoogle Scholar
  7. [7]
    Zheng M, Yang J, Xu X, Sebolt JT, Wang S, Sun Y. Efficacy of MDM2 inhibitor MI-219 against lung cancer cells alone or in combination with MDM2 knockdown, a XIAP inhibitor or etoposide. Anticancer Res. 2010, 30(9):3321–3331PubMedGoogle Scholar
  8. [8]
    Li J, Poi MJ, Tsai MD. Regulatory mechanisms of tumor suppressor P16(INK4A) and their relevance to cancer. Biochemistry. 2011, 50(25):5566–5582PubMedCentralPubMedCrossRefGoogle Scholar
  9. [9]
    Ota N, Kawakami K, Okuda T, Takehara A, Hiranuma C, Oyama K, Ota Y, Oda M, Watanabe G. Prognostic significance of p16(INK4a) hypermethylation in non-small cell lung cancer is evident by quantitative DNA methylation analysis. Anticancer Res. 2006, 26(5B):3729–3732PubMedGoogle Scholar
  10. [10]
    Yoshino M, Suzuki M, Tian L, Moriya Y, Hoshino H, Okamoto T, Yoshida S, Shibuya K, Yoshino I. Promoter hypermethylation of the p16 and Wif-1 genes as an independent prognostic marker in stage IA non-small cell lung cancers. Int J Oncol. 2009, 35(5):1201–1209PubMedGoogle Scholar
  11. [11]
    Gazdar AF. Activating and resistance mutations of EGFR in non-small-cell lung cancer: role in clinical response to EGFR tyrosine kinase inhibitors. Oncogene. 2009; 28 Suppl 1:S24–S31CrossRefGoogle Scholar
  12. [12]
    da Cunha Santos G, Shepherd FA, Tsao MS. EGFR mutations and lung cancer. Annu Rev Pathol. 2011, 6:49–69PubMedCrossRefGoogle Scholar
  13. [13]
    Bittner N, Ostoros G, Geczi L. New treatment options for lung adenocarcinoma — in view of molecular background. Pathol Oncol Res. 2013, 10.1007/ s12253-013-9719-9719Google Scholar
  14. [14]
    Cappuzzo F, Ciuleanu T, Stelmakh L, Cicenas S, Szczesna A, Juhasz E, Esteban E, Molinier O, Brugger W, Melezinek I, Klingelschmitt G, Klughammer B, Giaccone G, SATURN investigators. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2010, 11(6):521–529PubMedCrossRefGoogle Scholar
  15. [15]
    Maemondo M, Minegishi Y, Inoue A, Kobayashi K, Harada M, Okinaga S, Morikawa N, Oizumi S, Tanaka T, Isobe H, Kudoh S, Haqiwara K, Nukiwa T, Gemma A. First-line gefitinib in patients aged 75 or older with advanced non-small cell lung cancer harboring epidermal growth factor receptor mutations: NEJ 003 study. J Thorac Oncol. 2012, 7(9):1417–1422PubMedCrossRefGoogle Scholar
  16. [16]
    Fukuoka M, Wu YL, Thonqprasert S, Sunpaweravong P, Leong SS, Sriuranpong V, Chao TY, Nakaqawa K, Chu DT, Saijo N, Duffield EL, Rukazenkov Y, Speake G, Jiang H, Armour AA, To KF, Yang JC, Mok TS. Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol. 2011, 29(21):2866–2874PubMedCrossRefGoogle Scholar
  17. [17]
    Mendez M, Custodio A, Provencio M. New molecular targeted therapies for advanced non-smallcell lung cancer. J Thorac Dis. 2011, 3(1):30–56PubMedCentralPubMedGoogle Scholar
  18. [18]
    Kosaka T, Yamaki E, Mogi A, Kuwano H. Mechanisms of resistance to EGFR TKIs and development of a new generation of drugs in nonsmall-cell lung cancer. J Biomed Biotechnol. 2011, 2011:165214PubMedCentralPubMedCrossRefGoogle Scholar
  19. [19]
    Sasaki T, Rodig SJ, Chirieac LR, Jänne PA. The biology and treatment of EMLK4-ALK non-small cell lung cancer. Eur J Cancer. 2010, 46(10):1773–1780PubMedCentralPubMedCrossRefGoogle Scholar
  20. [20]
    Shaw AT, Solomon B. Targeting anaplastic lymphoma kinase in lung cancer. Clin Cancer Res. 2011, 17(8):2081–2086PubMedCrossRefGoogle Scholar
  21. [21]
    Wu SG, Kyo YW, Chang YL, Shih JY, Chen YH, Tsai MF, Yu CJ, Yang CH, Yang PC. EML4-ALK translocation predicts better outcome in lung adenocarcinoma patients with wild-type EGFR. J Thorac Oncol. 2012; 7(1):98–104PubMedCrossRefGoogle Scholar
  22. [22]
    Camidge DR, Bang YJ, Kwak EL, Iafrate AJ, Varella-Garcia M, Fox SB, Riely GJ, Solomon B, Ou SH, Kim DW, Salgia R, Fidias P, Engelman JA, Gandhi L, Janne PA, Costa DB, Shapiro GI, Lorusso P, Ruffner K, Stephenson P, Tang Y, Wilner K, Clark JW, Shaw AT. Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study. Lancet Oncol. 2012, 13(10):1011–1019PubMedCentralPubMedCrossRefGoogle Scholar
  23. [23]
    Zhang GB, Chen J, Wang LR, Li J, Li MW, Xu N, Wang Y, Shentu JZ. RRM1 and ERCC1 expression in peripheral blood versus tumor tissue in gemcitabine/ carboplatin-treated advanced non-small cell lung cancer. Cancer Chemother Pharmacol. 2012, 69(5):1277–1287PubMedCrossRefGoogle Scholar
  24. [24]
    Olaussen KA, Dunant A, Fouret P, Brambilla E, Andre F, Haddad V, Taranchon E, Filipits M, Pirker R, Popper HH, Stahel R, Sabatier L, Pignon JP, Tursz T, Le Chevalier T, Soria JC, IALT Bio Investigators. DNA repair by ERCC1 in non-smallcell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med. 2006, 355(10):983–991PubMedCrossRefGoogle Scholar
  25. [25]
    Allingham-Hawkins D, Lea A, Levine S. ERCC1 expression analysis to guide therapy in non-small cell lung cancer. PLoS Curr. 2010, 2:RRN1202PubMedCentralPubMedGoogle Scholar
  26. [26]
    Zheng Z, Chen T, Li X, Haura E, Sharma A, Bepler G. DNA synthesis and repair genes RRM1 and ERCC1 in lung cancer. N Engl J Med. 2007, 356(8):800–808PubMedCrossRefGoogle Scholar
  27. [27]
    Simon GR, Schell MJ, Begum M, Kim J, Chiappori A, Haura E, Antonia S, Bepler G. 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. 2012, 118(9):2525–2531PubMedCentralPubMedCrossRefGoogle Scholar
  28. [28]
    Karachaliou N, Mayo C, Costa C, Magri I, Gimenez-Capitan A, Molina-Vila MA, Rosell R. KRAS mutations in lung cancer. Clin Lung Cancer. 2013, 14(3):205–214PubMedCrossRefGoogle Scholar
  29. [29]
    Guan JL, Zhoang WZ, An SJ, Yang JJ, Su J, Chen ZH, Yan HH, Chen ZY, Huang ZM, Zhang XC, Nie Q, Wu YL. KRAS mutation in patients with lung cancer: a predictor for poor prognosis but not for EGFR-TKIs or chemotherapy. Ann Surg Oncol. 2013, 20(4):1381–1388PubMedCrossRefGoogle Scholar
  30. [30]
    Aviel-Ronen S, Blackhall FH, Shepherd FA, Tsao M-S. K-ras mutations in non-small-cell lung carcinoma: a review. Clin Lung Cancer. 2006, 8(1):30–38PubMedCrossRefGoogle Scholar
  31. [31]
    Eberhard DA, Johnson BE, Amler LC, Goddard AD, Heldens SL, Herbst RS, Ince WL, Janne PA, Januario T, Johnson DH, Klein P, Miller VA, Ostland MA, Ramies DA, Sebisanovic D, Stinson JA, Zhang YR, Seshagiri S, Hillan KJ. Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol. 2005, 23(25):5900–5909PubMedCrossRefGoogle Scholar
  32. [32]
    Brugger W, Triller N, Blasinska-Morawiec M, Curescu S, Sakalauskas R, Manikhas GM, Mazieres J, Whittom R, Ward C, Mayne K, Trunzer K, Cappuzzo F. Prospective molecular marker analysis of EGFR and KRAS from a randomized, placebo-controlled study of erlotinib maintenance therapy in advanced non-small-cell lung cancer. J Clin Oncol. 2011, 29(31):4113–4120PubMedCrossRefGoogle Scholar
  33. [33]
    Carbone DP, Ciernik IF, Kelley MJ, Smith MC, Nadaf S, Kavanaugh D, Maher VE, Stipanov M, Contois D, Johnson BE, Pendleton CD, Seifert B, Carter C, Read EJ, Greenblatt J, Top LE, Kelsey MI, Minna JD, Berzofsky JA. Immunization with mutant p53-and K-ras-derived peptides in cancer patients: immune response and clinical outcome. J Clin Oncol. 2005, 23(22):5099–5107PubMedCrossRefGoogle Scholar
  34. [34]
    Acquaviva J, Smith DL, Sang J, Friedland JC, He S, Sequeira M, Zhang C, Wada Y, Proia DA. Targeting KRAS-mutant non-small cell lung cancer with the Hsp90 inhibitor ganetespib. Mol Cancer Ther. 2012, 11(12):2633–2643PubMedCrossRefGoogle Scholar
  35. [35]
    Dingemans AM, Mellema WW, Groen HJ, van Wijk A, Burgers SA, Kunst PW, Thunnissen E, Heideman DA, Smit EF. A phase II study of sorafenib in patients with platinum-pretreated, advanced (stage IIIb or IV) non-small cell lung cancer with a KRAS mutation. Clin Cancer Res. 2013, 19(3):743–751PubMedCrossRefGoogle Scholar
  36. [36]
    Jänne PA, Shaw AT, Pereira JR, Jeannin G, Vansteenkiste J, Barrios C, Franke FA, Grinsted L, Zazulina V, Smith P, Smith I, Crino L. Selumetinib plus docetaxel for KRAS-mutant advanced nonsmall-cell lung cancer: a randomized, multicenter, placebo-controlled, phase 2 study. Lancet Oncol. 2013, 14(1):38–47PubMedCrossRefGoogle Scholar
  37. [37]
    Enfield KS, Pikor LA, Martinez VD, Lam WL. Mechanistic roles of noncoding RNAs in lung cancer biology and their clinical implications. Genet Res Int. 2012, 2012:737416PubMedCentralPubMedGoogle Scholar
  38. [38]
    Wang R, Wang ZX, Yang JS, Pan X, De W, Chen LB. MicroRNA-451 functions as a tumor suppressor in human non-small cell lung cancer by targeting ras-related protein 14 (RAB14). Oncogene. 2011, 30(23):2644–2658PubMedCrossRefGoogle Scholar
  39. [39]
    Liu X, Lu KH, Wang KM, Sun M, Zhang EB, Yang JS, Yin DD, Liu ZL, Zhou J, Liu ZJ, De W, Wang ZX. MicroRNA-196a promotes non-small cell lung cancer cell proliferation and invasion through targeting HOXA5. BMC Cancer. 2012, 12:348PubMedCentralPubMedCrossRefGoogle Scholar
  40. [40]
    Yuxia M, Zhennan T, Wei Z. Circulating miR-125b is a novel biomarker for screening non-small-cell lung cancer and predicts poor prognosis. J Cancer Res Clin Oncol. 2012, 138(12):2045–2050PubMedCrossRefGoogle Scholar
  41. [41]
    Jusufovic E, Rijavec M, Keser D, Korosec P, Sodja E, Iljazovic E, Radojevic Z, Kosnik M. let-7b and miR-126 are down-regulated in tumor tissue and correlate with microvessel density and survival outcomes in non-small-cell lung cancer. PLoS One. 2012, 7(9):e45577PubMedCentralPubMedCrossRefGoogle Scholar
  42. [42]
    Navarro A, Diaz T, Gallardo E, Vinolas N, Marrades RM, Gel B, Campayo M, Quera A, Bandres E, Garcia-Foncillas J, Ramirez J, Monzo M. Prognostic implications of miR-16 expression levels in resected non-small-cell lung cancer. J Surg Oncol. 2011, 103(5):411–415PubMedCrossRefGoogle Scholar
  43. [43]
    Yu SL, Chen HY, Chang GC, Chen CY, Chen HW, Singh S, Cheng CL, Yu CJ, Lee YC, Chen HS, Su TJ, Chiang CC, Li HN, Hong QS, Su HY, et al. MicroRNA signature predicts survival and relapse in lung cancer. Cancer Cell. 2008, 13(1):48–57PubMedCrossRefGoogle Scholar
  44. [44]
    Gao W, Xu J, Shu Y. miRNA expression and its clinical implications for the prevention and diagnosis of non-small-cell lung cancer. Expert Rev Respir Med. 2011, 5(5):699–709PubMedCrossRefGoogle Scholar
  45. [45]
    Wan G, Mathur R, Hu X, Zhang X, Lu X. miRNA response to DNA damage. Trends Biochem Sci. 2011, 36(9):478–484PubMedCentralPubMedCrossRefGoogle Scholar
  46. [46]
    Galluzzi L, Morselli E, Vitale I, Kepp O, Senovilla L, Criollo A, Servant N, Paccard C, Hupe P, Robert T, Ripoche H, Lazar V, Harel-Bellan A, Dessen P, Barillot E, Kroemer G. miR-181a and miR-630 regulate cisplatin-induced cancer cell death. Cancer Res. 2010, 70(5):1793–1803PubMedCrossRefGoogle Scholar
  47. [47]
    Wei J, Gao W, Zhu CJ, Liu YQ, Mei Z, Cheng T, Shu YQ. Identification of plasma microRNA-21 as a biomarker for early detection and chemosensitivity of non-small cell lung cancer. Chin J Cancer. 2011, 30(6):407–414PubMedCentralPubMedCrossRefGoogle Scholar
  48. [48]
    van der Drift MA, Hol BE, Klaassen CH, Prinsen CF, van Aarssen YA, Donders R, van der Stappen JW, Dekhuijzen PN, van der Heijden HF, Thunnissen FB. Circulating DNA is a non-invasive prognostic factor for survival in non-small cell lung cancer. Lung Cancer. 2010, 68(2):283–287PubMedCrossRefGoogle Scholar
  49. [49]
    Catarino R, Coelho A, Araujo A, Gomes M, Nogueira A, Lopes C, Medeiros R. Circulating DNA: diagnostic tool and predictive marker for overall survival of NSCLC patients. PLoS One. 2012, 7(6):e38559PubMedCentralPubMedCrossRefGoogle Scholar
  50. [50]
    Kumar S, Guleria R, Singh V, Bharti AC, Mohan A, Das BC. Efficacy of circulating plasma DNA as a diagnostic tool for advanced non-small cell lung cancer and its predictive utility for survival and response to chemotherapy. Lung Cancer. 2010, 70(2):211–217PubMedCrossRefGoogle Scholar
  51. [51]
    Ludovini V, Pistola L, Gregorc V, Floriani I, Rulli E, Piattoni S, Di Carlo L, Semeraro A, Darwish S, Tofanetti FR, Stocchi L, Mihaylova Z, Bellezza G, Del Sordo R, Daddi G, Crino L, Tonato M. Plasma DNA, microsatellite alterations, and p53 tumor mutations are associated with disease-free survival in radically resected non-small cell lung cancer patients. J Thorac Oncol. 2008, 3(4):365–373PubMedCrossRefGoogle Scholar
  52. [52]
    Gautschi O, Bigosch C, Huegli B, Jermann M, Marx A, Chasse E, Ratschiller D, Weder W, Joerger M, Betticher DC, Stahel RA, Ziegler A. Circulating deoxyribonucleic acid as prognostic marker in nonsmall-cell lung cancer patients undergoing chemotherapy. J Clin Oncol. 2004, 22(20):4157–4164PubMedCrossRefGoogle Scholar
  53. [53]
    O’Flaherty JD, Gray S, Richard D, Fennell D, O’Leary JJ, Blackhall FH, O’Byrne KJ. Circulating tumour cells, their role in metastasis and their clinical utility in lung cancer. Lung Cancer. 2012, 76(1):19–25PubMedCrossRefGoogle Scholar
  54. [54]
    Tanaka F, Yoneda K, Hasegawa S. Circulating tumor cells (CTCs) in lung cancer: current status and future perspectives. Lung Cancer: Targets and Therapy. 2010, 1:77–84Google Scholar
  55. [55]
    Krebs MG, Sloane R, Priest L, Lancashire L, Hou JM, Greystoke A, Ward TH, Ferraldeschi R, Hughes A, Clack G, Ranson M, Dive C, Blackhall FH. Evaluation and prognostic significance of circulating tumor cells in patients with non-small-cell lung cancer. J Clin Oncol. 2011, 29(12):1556–1563PubMedCrossRefGoogle Scholar
  56. [56]
    Nieva J, Wendel M, Luttgen MS, Marrinucci D, Bazhenova L, Kolatkar A, Santala R, Whittenberger B, Burke J, Torrey M, Bethel K, Kuhn P. Highdefinition imaging of circulating tumor cells and associated cellular events in non-small cell lung cancer patients: a longitudinal analysis. Phys Biol. 2012, 9(1):016004PubMedCentralPubMedCrossRefGoogle Scholar
  57. [57]
    Das M, Riess JW, Frankel P, Schwartz E, Bennis R, Hsieh HB, Liu X, Ly JC, Zhou L, Nieva JJ, Wakelee HA, Bruce RH. ERCC1 expression in circulating tumor cells (CTCs) using a novel detection platform correlates with progression-free survival (PFS) in patients with metastatic non-small-cell lung cancaer (NSCLC) receiving platinum chemotherapy. Lung Cancer. 2012, 77(2):421–426PubMedCrossRefGoogle Scholar

Copyright information

© Versita Warsaw and Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Diana Schveigert
    • 1
  • Saulius Cicenas
    • 1
    • 2
  • Jaroslav Bublevic
    • 2
  • Renatas Askinis
    • 1
    • 2
  • Virginijus Sapoka
    • 1
    • 2
  • Janina Didziapetriene
    • 1
    • 2
  1. 1.Institute of OncologyVilnius UniversityVilniusLithuania
  2. 2.Faculty of MedicineVilnius UniversityVilniusLithuania

Personalised recommendations