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Open Access 01-12-2013 | Review

Bridging the clinical gaps: genetic, epigenetic and transcriptomic biomarkers for the early detection of lung cancer in the post-National Lung Screening Trial era

Authors: John F Brothers, Kahkeshan Hijazi, Celine Mascaux, Randa A El-Zein, Margaret R Spitz, Avrum Spira

Published in: BMC Medicine | Issue 1/2013

Abstract

Lung cancer is the leading cause of cancer death worldwide in part due to our inability to identify which smokers are at highest risk and the lack of effective tools to detect the disease at its earliest and potentially curable stage. Recent results from the National Lung Screening Trial have shown that annual screening of high-risk smokers with low-dose helical computed tomography of the chest can reduce lung cancer mortality. However, molecular biomarkers are needed to identify which current and former smokers would benefit most from annual computed tomography scan screening in order to reduce the costs and morbidity associated with this procedure. Additionally, there is an urgent clinical need to develop biomarkers that can distinguish benign from malignant lesions found on computed tomography of the chest given its very high false positive rate. This review highlights recent genetic, transcriptomic and epigenomic biomarkers that are emerging as tools for the early detection of lung cancer both in the diagnostic and screening setting.

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Patel JD, Bach PB, Kris MG: Lung cancer in US women: a contemporary epidemic. JAMA. 2004, 291: 1763-1768. 10.1001/jama.291.14.1763.PubMed

Patel JD: Lung cancer in women. J Clin Oncol. 2005, 23: 3212-3218. 10.1200/JCO.2005.11.486.PubMed

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin. 2011, 61: 69-90. 10.3322/caac.20107.PubMed

Jemal A, Center MM, DeSantis C, Ward EM: Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev. 2010, 19: 1893-1907. 10.1158/1055-9965.EPI-10-0437.PubMed

Collins LG, Haines C, Perkel R, Enck RE: Lung cancer: diagnosis and management. Am Fam Physician. 2007, 75: 56-63.PubMed

Shopland DR, Burns DM: Changes in cigarette-related disease risks and their implications for prevention and control. Volume 8 of Smoking and Tobacco Control Monographs. 1997, Bethesda, MD: National Institutes of Health/National Cancer Institute

Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, Fagerstrom RM, Gareen IF, Gatsonis C, Marcus PM, Sicks JD, National Lung Screening Trial Research Team: Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011, 365: 395-409.PubMed

Hassanein M, Callison JC, Callaway-Lane C, Aldrich MC, Grogan EL, Massion PP: The state of molecular biomarkers for the early detection of lung cancer. Cancer Prev Res (Phila). 2012, 5: 992-1006. 10.1158/1940-6207.CAPR-11-0441.

Amos CI, Wu X, Broderick P, Gorlov IP, Gu J, Eisen T, Dong Q, Zhang Q, Gu X, Vijayakrishnan J, Sullivan K, Matakidou A, Wang Y, Mills G, Doheny K, Tsai YY, Chen WV, Shete S, Spitz MR, Houlston RS: Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nat Genet. 2008, 40: 616-622. 10.1038/ng.109.PubMedPubMedCentral

10.

Hung RJ, McKay JD, Gaborieau V, Boffetta P, Hashibe M, Zaridze D, Mukeria A, Szeszenia-Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Mates D, Bencko V, Foretova L, Janout V, Chen C, Goodman G, Field JK, Liloglou T, Xinarianos G, Cassidy A, McLaughlin J, Liu G, Narod S, Krokan HE, Skorpen F, Elvestad MB, Hveem K, Vatten L, Linseisen J, et al: A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25. Nature. 2008, 452: 633-637. 10.1038/nature06885.PubMed

11.

Thorgeirsson TE, Gudbjartsson DF, Surakka I, Vink JM, Amin N, Geller F, et al: Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior. Nat Genet. 2010, 42: 448-453. 10.1038/ng.573.PubMedPubMedCentral

12.

Landi MT, Chatterjee N, Yu K, Goldin LR, Goldstein AM, Rotunno M, et al: A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma. Am J Hum Genet. 2009, 85: 679-691. 10.1016/j.ajhg.2009.09.012.PubMedPubMedCentral

13.

Saccone NL, Culverhouse RC, Schwantes-An TH, Cannon DS, Chen X, Cichon S, et al: Multiple independent loci at chromosome 15q25.1 affect smoking quantity: a meta-analysis and comparison with lung cancer and COPD. PLoS Genet. 2010, 6: e1001053-10.1371/journal.pgen.1001053.PubMedPubMedCentral

14.

Liu JZ, Tozzi F, Waterworth DM, Pillai SG, Muglia P, Middleton L, et al: Meta-analysis and imputation refines the association of 15q25 with smoking quantity. Nat Genet. 2010, 42: 436-440. 10.1038/ng.572.PubMedPubMedCentral

15.

Tobacco and Genetics Consortium: Genome-wide meta-analyses identify multiple loci associated with smoking behavior. Nat Genet. 2010, 42: 441-447. 10.1038/ng.571.

16.

Spitz MR, Amos CI, Dong Q, Lin J, Wu X: The CHRNA5-A3 region on chromosome 15q24-25.1 is a risk factor both for nicotine dependence and for lung cancer. J Natl Cancer Inst. 2008, 100: 1552-1556. 10.1093/jnci/djn363.PubMedPubMedCentral

17.

Wang Y, Broderick P, Matakidou A, Eisen T, Houlston RS: Chromosome 15q25 (CHRNA3-CHRNA5) variation impacts indirectly on lung cancer risk. PLoS One. 2011, 6: e19085-10.1371/journal.pone.0019085.PubMedPubMedCentral

18.

Spitz MR, Amos CI, Bierut LJ, Caporaso NE: Cotinine conundrum–a step forward but questions remain. J Natl Cancer Inst. 2012, 104: 720-722. 10.1093/jnci/djs211.PubMedPubMedCentral

19.

Truong T, Hung RJ, Amos CI, Wu X, Bickeboller H, Rosenberger A, Sauter W, Illig T, Wichmann HE, Risch A, Dienemann H, Kaaks R, Yang P, Jiang R, Wiencke JK, Wrensch M, Hansen H, Kelsey KT, Matsuo K, Tajima K, Schwartz AG, Wenzlaff A, Seow A, Ying C, Staratschek-Jox A, Nürnberg P, Stoelben E, Wolf J, Lazarus P, Muscat JE, et al: Replication of lung cancer susceptibility loci at chromosomes 15q25, 5p15, and 6p21: a pooled analysis from the International Lung Cancer Consortium. J Natl Cancer Inst. 2010, 102: 959-971. 10.1093/jnci/djq178.PubMedPubMedCentral

20.

Galvan A, Dragani TA: Nicotine dependence may link the 15q25 locus to lung cancer risk. Carcinogenesis. 2010, 31: 331-333. 10.1093/carcin/bgp282.PubMed

21.

Zou P, Gu A, Ji G, Zhao L, Zhao P, Lu A: The TERT rs2736100 polymorphism and cancer risk: a meta-analysis based on 25 case–control studies. BMC Cancer. 2012, 12: 7-10.1186/1471-2407-12-7.PubMedPubMedCentral

22.

Spitz MR, Amos CI, Land S, Wu X, Dong Q, Wenzlaff AS, Schwartz AG: Role of select genetic variants in lung cancer risk in African Americans. J Thorac Oncol. 2013, 8: 391-397. 10.1097/JTO.0b013e318283da29.PubMedPubMedCentral

23.

Melin BS, Nordfjall K, Andersson U, Roos G: hTERT cancer risk genotypes are associated with telomere length. Genet Epidemiol. 2012, 36: 368-372. 10.1002/gepi.21630.PubMed

24.

Zhu CQ, Cutz JC, Liu N, Lau D, Shepherd FA, Squire JA, Tsao MS: Amplification of telomerase (hTERT) gene is a poor prognostic marker in non-small-cell lung cancer. Br J Cancer. 2006, 94: 1452-1459. 10.1038/sj.bjc.6603110.PubMedPubMedCentral

25.

James MA, Wen W, Wang Y, Byers LA, Heymach JV, Coombes KR, Girard L, Minna J, You M: Functional characterization of CLPTM1L as a lung cancer risk candidate gene in the 5p15.33 locus. PLoS One. 2012, 7: e36116-10.1371/journal.pone.0036116.PubMedPubMedCentral

26.

Wang Y, Broderick P, Webb E, Wu X, Vijayakrishnan J, Matakidou A, Qureshi M, Dong Q, Gu X, Chen WV, Spitz MR, Eisen T, Amos CI, Houlston RS: Common 5p15.33 and 6p21.33 variants influence lung cancer risk. Nat Genet. 2008, 40: 1407-1409. 10.1038/ng.273.PubMedPubMedCentral

27.

Bae EY, Lee SY, Kang BK, Lee EJ, Choi YY, Kang HG, Choi JE, Jeon HS, Lee WK, Kam S, Shin KM, Jin G, Yoo SS, Lee J, Cha SI, Kim CH, Jung TH, Park JY: Replication of results of genome-wide association studies on lung cancer susceptibility loci in a Korean population. Respirology. 2012, 17: 699-706. 10.1111/j.1440-1843.2012.02165.x.PubMed

28.

Shiraishi K, Kunitoh H, Daigo Y, Takahashi A, Goto K, Sakamoto H, Ohnami S, Shimada Y, Ashikawa K, Saito A, Watanabe S, Tsuta K, Kamatani N, Yoshida T, Nakamura Y, Yokota J, Kubo M, Kohno T: A genome-wide association study identifies two new susceptibility loci for lung adenocarcinoma in the Japanese population. Nat Genet. 2012, 44: 900-903. 10.1038/ng.2353.PubMed

29.

Hu Z, Wu C, Shi Y, Guo H, Zhao X, Yin Z, Yang L, Dai J, Hu L, Tan W, Li Z, Deng Q, Wang J, Wu W, Jin G, Jiang Y, Yu D, Zhou G, Chen H, Guan P, Chen Y, Shu Y, Xu L, Liu X, Liu L, Xu P, Han B, Bai C, Zhao Y, Zhang H, et al: A genome-wide association study identifies two new lung cancer susceptibility loci at 13q12.12 and 22q12.2 in Han Chinese. Nat Genet. 2011, 43: 792-796. 10.1038/ng.875.PubMed

30.

Dong J, Hu Z, Wu C, Guo H, Zhou B, Lv J, Lu D, Chen K, Shi Y, Chu M, Wang C, Zhang R, Dai J, Jiang Y, Cao S, Qin Z, Yu D, Ma H, Jin G, Gong J, Sun C, Zhao X, Yin Z, Yang L, Li Z, Deng Q, Wang J, Wu W, Zheng H, Zhou G, et al: Association analyses identify multiple new lung cancer susceptibility loci and their interactions with smoking in the Chinese population. Nat Genet. 2012, 44: 895-899. 10.1038/ng.2351.PubMed

31.

Jin G, Ma H, Wu C, Dai J, Zhang R, Shi Y, Lu J, Miao X, Wang M, Zhou Y, Chen J, Li H, Pan S, Chu M, Lu F, Yu D, Jiang Y, Dong J, Hu L, Chen Y, Xu L, Shu Y, Pan S, Tan W, Zhou B, Lu D, Wu T, Zhang Z, Chen F, Wang X, et al: Genetic variants at 6p21.1 and 7p15.3 are associated with risk of multiple cancers in Han Chinese. Am J Hum Genet. 2012, 91: 928-934. 10.1016/j.ajhg.2012.09.009.PubMedPubMedCentral

32.

Shi J, Chatterjee N, Rotunno M, Wang Y, Pesatori AC, Consonni D, Li P, Wheeler W, Broderick P, Henrion M, Eisen T, Wang Z, Chen W, Dong Q, Albanes D, Thun M, Spitz MR, Bertazzi PA, Caporaso NE, Chanock SJ, Amos CI, Houlston RS, Landi MT: Inherited variation at chromosome 12p13.33, including RAD52, influences the risk of squamous cell lung carcinoma. Cancer Discov. 2012, 2: 131-139. 10.1158/2159-8290.CD-11-0246.PubMed

33.

Tammimaki A, Horton WJ, Stitzel JA: Recent advances in gene manipulation and nicotinic acetylcholine receptor biology. Biochem Pharmacol. 2011, 82: 808-819. 10.1016/j.bcp.2011.06.014.PubMedPubMedCentral

34.

De BM, Dani JA: Reward, addiction, withdrawal to nicotine. Annu Rev Neurosci. 2011, 34: 105-130. 10.1146/annurev-neuro-061010-113734.

35.

Liu Y, Liu P, Wen W, James MA, Wang Y, Bailey-Wilson JE, Amos CI, Pinney SM, Yang P, de Andrade M, Petersen GM, Wiest JS, Fain PR, Schwartz AG, Gazdar A, Gaba C, Rothschild H, Mandal D, Kupert E, Lee J, Seminara D, Minna J, Anderson MW, You M: Haplotype and cell proliferation analyses of candidate lung cancer susceptibility genes on chromosome 15q24-25.1. Cancer Res. 2009, 69: 7844-7850. 10.1158/0008-5472.CAN-09-1833.PubMedPubMedCentral

36.

Maisonneuve P, Bagnardi V, Bellomi M, Spaggiari L, Pelosi G, Rampinelli C, Bertolotti R, Rotmensz N, Field JK, Decensi A, Veronesi G: Lung cancer risk prediction to select smokers for screening CT–a model based on the Italian COSMOS trial. Cancer Prev Res (Phila). 2011, 4: 1778-1789. 10.1158/1940-6207.CAPR-11-0026.

37.

Tammemagi CM, Pinsky PF, Caporaso NE, Kvale PA, Hocking WG, Church TR, Riley TL, Commins J, Oken MM, Berg CD, Prorok PC: Lung cancer risk prediction: Prostate, Lung, Colorectal And Ovarian Cancer Screening Trial models and validation. J Natl Cancer Inst. 2011, 103: 1058-1068. 10.1093/jnci/djr173.PubMedPubMedCentral

38.

Cassidy A, Myles JP, van Tongeren M, Page RD, Liloglou T, Duffy SW, Field JK: The LLP risk model: an individual risk prediction model for lung cancer. Br J Cancer. 2008, 98: 270-276. 10.1038/sj.bjc.6604158.PubMed

39.

Spitz MR, Hong WK, Amos CI, Wu X, Schabath MB, Dong Q, Shete S, Etzel CJ: A risk model for prediction of lung cancer. J Natl Cancer Inst. 2007, 99: 715-726. 10.1093/jnci/djk153.PubMed

40.

Bach PB, Kattan MW, Thornquist MD, Kris MG, Tate RC, Barnett MJ, Hsieh LJ, Begg CB: Variations in lung cancer risk among smokers. J Natl Cancer Inst. 2003, 95: 470-478. 10.1093/jnci/95.6.470.PubMed

41.

Young RP, Hopkins RJ, Whittington CF, Hay BA, Epton MJ, Gamble GD: Individual and cumulative effects of GWAS susceptibility loci in lung cancer: associations after sub-phenotyping for COPD. PLoS One. 2011, 6: e16476-10.1371/journal.pone.0016476.PubMedPubMedCentral

42.

Wilk JB, Walter RE, Laramie JM, Gottlieb DJ, O’Connor GT: Framingham Heart Study genome-wide association: results for pulmonary function measures. BMC Med Genet. 2007, 8: S8-10.1186/1471-2350-8-S1-S8.PubMedPubMedCentral

43.

Hancock DB, Eijgelsheim M, Wilk JB, Gharib SA, Loehr LR, Marciante KD, Franceschini N, van Durme YM, Chen TH, Barr RG, Schabath MB, Couper DJ, Brusselle GG, Psaty BM, van Duijn CM, Rotter JI, Uitterlinden AG, Hofman A, Punjabi NM, Rivadeneira F, Morrison AC, Enright PL, North KE, Heckbert SR, Lumley T, Stricker BH, O’Connor GT, London SJ: Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function. Nat Genet. 2010, 42: 45-52. 10.1038/ng.500.PubMed

44.

Repapi E, Sayers I, Wain LV, Burton PR, Johnson T, Obeidat M, Zhao JH, Ramasamy A, Zhai G, Vitart V, Huffman JE, Igl W, Albrecht E, Deloukas P, Henderson J, Granell R, McArdle WL, Rudnicka AR, Wellcome Trust Case Control C, Barroso I, Loos RJ, Wareham NJ, Mustelin L, Rantanen T, Surakka I, Imboden M, Wichmann HE, Grkovic I, Jankovic S, Zgaga L, et al: Genome-wide association study identifies five loci associated with lung function. Nat Genet. 2010, 42: 36-44. 10.1038/ng.501.PubMed

45.

Pillai SG, Ge D, Zhu G, Kong X, Shianna KV, Need AC, Feng S, Hersh CP, Bakke P, Gulsvik A, Ruppert A, Lødrup Carlsen KC, Roses A, Anderson W, Rennard SI, Lomas DA, Silverman EK, Goldstein DB, ICGN Investigators: A genome-wide association study in chronic obstructive pulmonary disease (COPD): identification of two major susceptibility loci. PLoS Genet. 2009, 5: e1000421-10.1371/journal.pgen.1000421.PubMedPubMedCentral

46.

Wilk JB, Chen TH, Gottlieb DJ, Walter RE, Nagle MW, Brandler BJ, Myers RH, Borecki IB, Silverman EK, Weiss ST, O’Connor GT: A genome-wide association study of pulmonary function measures in the Framingham Heart Study. PLoS Genet. 2009, 5: e1000429-10.1371/journal.pgen.1000429.PubMedPubMedCentral

47.

Broderick P, Wang Y, Vijayakrishnan J, Matakidou A, Spitz MR, Eisen T, Amos CI, Houlston RS: Deciphering the impact of common genetic variation on lung cancer risk: a genome-wide association study. Cancer Res. 2009, 69: 6633-6641. 10.1158/0008-5472.CAN-09-0680.PubMedPubMedCentral

48.

Thorgeirsson TE, Geller F, Sulem P, Rafnar T, Wiste A, Magnusson KP, Manolescu A, Thorleifsson G, Stefansson H, Ingason A, Stacey SN, Bergthorsson JT, Thorlacius S, Gudmundsson J, Jonsson T, Jakobsdottir M, Saemundsdottir J, Olafsdottir O, Gudmundsson LJ, Bjornsdottir G, Kristjansson K, Skuladottir H, Isaksson HJ, Gudbjartsson T, Jones GT, Mueller T, Gottsäter A, Flex A, Aben KK, de Vegt F, et al: A variant associated with nicotine dependence, lung cancer and peripheral arterial disease. Nature. 2008, 452: 638-642. 10.1038/nature06846.PubMedPubMedCentral

49.

Cho MH, Castaldi PJ, Wan ES, Siedlinski M, Hersh CP, Demeo DL, Himes BE, Sylvia JS, Klanderman BJ, Ziniti JP, Lange C, Litonjua AA, Sparrow D, Regan EA, Make BJ, Hokanson JE, Murray T, Hetmanski JB, Pillai SG, Kong X, Anderson WH, Tal-Singer R, Lomas DA, Coxson HO, Edwards LD, MacNee W, Vestbo J, Yates JC, Agusti A, Calverley PM, et al: A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13. Hum Mol Genet. 2012, 21: 947-957. 10.1093/hmg/ddr524.PubMed

50.

Wang J, Spitz MR, Amos CI, Wilkinson AV, Wu X, Shete S: Mediating effects of smoking and chronic obstructive pulmonary disease on the relation between the CHRNA5-A3 genetic locus and lung cancer risk. Cancer. 2010, 116: 3458-3462. 10.1002/cncr.25085.PubMedPubMedCentral

51.

Young RP, Hopkins RJ: How the genetics of lung cancer may overlap with COPD. Respirology. 2011, 16: 1047-1055. 10.1111/j.1440-1843.2011.02019.x.PubMed

52.

El-Zein RA, Young RP, Hopkins RJ, Etzel CJ: Genetic predisposition to chronic obstructive pulmonary disease and/or lung cancer: important considerations when evaluating risk. Cancer Prev Res (Phila). 2012, 5: 522-527. 10.1158/1940-6207.CAPR-12-0042.

53.

Bird A: Perceptions of epigenetics. Nature. 2007, 447: 396-398. 10.1038/nature05913.PubMed

54.

Bird A: DNA methylation patterns and epigenetic memory. Genes Dev. 2002, 16: 6-21. 10.1101/gad.947102.PubMed

55.

Robertson KD: DNA methylation and human disease. Nat Rev Genet. 2005, 6: 597-610.PubMed

56.

Shames DS, Girard L, Gao B, Sato M, Lewis CM, Shivapurkar N, Jiang A, Perou CM, Kim YH, Pollack JR, Fong KM, Lam CL, Wong M, Shyr Y, Nanda R, Olopade OI, Gerald W, Euhus DM, Shay JW, Gazdar AF, Minna JD: A genome-wide screen for promoter methylation in lung cancer identifies novel methylation markers for multiple malignancies. PLoS Med. 2006, 3: e486-10.1371/journal.pmed.0030486.PubMedPubMedCentral

57.

Field JK, Liloglou T, Warrak S, Burger M, Becker E, Berlin K, Nimmrich I, Maier S: Methylation discriminators in NSCLC identified by a microarray based approach. Int J Oncol. 2005, 27: 105-111.PubMed

58.

Wang L, Aakre JA, Jiang R, Marks RS, Wu Y, Chen J, Thibodeau SN, Pankratz VS, Yang P: Methylation markers for small cell lung cancer in peripheral blood leukocyte DNA. J Thorac Oncol. 2010, 5: 778-785. 10.1097/JTO.0b013e3181d6e0b3.PubMedPubMedCentral

59.

Belinsky SA, Nikula KJ, Palmisano WA, Michels R, Saccomanno G, Gabrielson E, Baylin SB, Herman JG: Aberrant methylation of p16(INK4a) is an early event in lung cancer and a potential biomarker for early diagnosis. Proc Natl Acad Sci USA. 1998, 95: 11891-11896. 10.1073/pnas.95.20.11891.PubMedPubMedCentral

60.

Palmisano WA, Divine KK, Saccomanno G, Gilliland FD, Baylin SB, Herman JG, Belinsky SA: Predicting lung cancer by detecting aberrant promoter methylation in sputum. Cancer Res. 2000, 60: 5954-5958.PubMed

61.

Belinsky SA, Klinge DM, Dekker JD, Smith MW, Bocklage TJ, Gilliland FD, Crowell RE, Karp DD, Stidley CA, Picchi MA: Gene promoter methylation in plasma and sputum increases with lung cancer risk. Clin Cancer Res. 2005, 11: 6505-6511. 10.1158/1078-0432.CCR-05-0625.PubMed

62.

Machida EO, Brock MV, Hooker CM, Nakayama J, Ishida A, Amano J, Picchi MA, Belinsky SA, Herman JG, Taniguchi S, Baylin SB: Hypermethylation of ASC/TMS1 is a sputum marker for late-stage lung cancer. Cancer Res. 2006, 66: 6210-6218. 10.1158/0008-5472.CAN-05-4447.PubMed

63.

Belinsky SA, Liechty KC, Gentry FD, Wolf HJ, Rogers J, Vu K, Haney J, Kennedy TC, Hirsch FR, Miller Y, Franklin WA, Herman JG, Baylin SB, Bunn PA, Byers T: Promoter hypermethylation of multiple genes in sputum precedes lung cancer incidence in a high-risk cohort. Cancer Res. 2006, 66: 3338-3344. 10.1158/0008-5472.CAN-05-3408.PubMed

64.

Leng S, Do K, Yingling CM, Picchi MA, Wolf HJ, Kennedy TC, Feser WJ, Baron AE, Franklin WA, Brock MV, Herman JG, Baylin SB, Byers T, Stidley CA, Belinsky SA: Defining a gene promoter methylation signature in sputum for lung cancer risk assessment. Clin Cancer Res. 2012, 18: 3387-3395. 10.1158/1078-0432.CCR-11-3049.PubMedPubMedCentral

65.

Leon SA, Shapiro B, Sklaroff DM, Yaros MJ: Free DNA in the serum of cancer patients and the effect of therapy. Cancer Res. 1977, 37: 646-650.PubMed

66.

Esteller M, Sanchez-Cespedes M, Rosell R, Sidransky D, Baylin SB, Herman JG: Detection of aberrant promoter hypermethylation of tumor suppressor genes in serum DNA from non-small cell lung cancer patients. Cancer Res. 1999, 59: 67-70.PubMed

67.

Fujiwara K, Fujimoto N, Tabata M, Nishii K, Matsuo K, Hotta K, Kozuki T, Aoe M, Kiura K, Ueoka H, Tanimoto M: Identification of epigenetic aberrant promoter methylation in serum DNA is useful for early detection of lung cancer. Clin Cancer Res. 2005, 11: 1219-1225.PubMed

68.

Lee SM, Park JY, Kim DS: Methylation of TMEFF2 gene in tissue and serum DNA from patients with non-small cell lung cancer. Mol Cells. 2012, 34: 171-176. 10.1007/s10059-012-0083-5.PubMedPubMedCentral

69.

Tan SH, Ida H, Lau QC, Goh BC, Chieng WS, Loh M, Ito Y: Detection of promoter hypermethylation in serum samples of cancer patients by methylation-specific polymerase chain reaction for tumour suppressor genes including RUNX3. Oncol Rep. 2007, 18: 1225-1230.PubMed

70.

Ulivi P, Zoli W, Calistri D, Fabbri F, Tesei A, Rosetti M, Mengozzi M, Amadori D: p16INK4A and CDH13 hypermethylation in tumor and serum of non-small cell lung cancer patients. J Cell Physiol. 2006, 206: 611-615. 10.1002/jcp.20503.PubMed

71.

Begum S, Brait M, Dasgupta S, Ostrow KL, Zahurak M, Carvalho AL, Califano JA, Goodman SN, Westra WH, Hoque MO, Sidransky D: An epigenetic marker panel for detection of lung cancer using cell-free serum DNA. Clin Cancer Res. 2011, 17: 4494-4503. 10.1158/1078-0432.CCR-10-3436.PubMedPubMedCentral

72.

Russo AL, Thiagalingam A, Pan H, Califano J, Cheng KH, Ponte JF, Chinnappan D, Nemani P, Sidransky D, Thiagalingam S: Differential DNA hypermethylation of critical genes mediates the stage-specific tobacco smoke-induced neoplastic progression of lung cancer. Clin Cancer Res. 2005, 11: 2466-2470. 10.1158/1078-0432.CCR-04-1962.PubMed

73.

Yang P, Ma J, Zhang B, Duan H, He Z, Zeng J, Zeng X, Li D, Wang Q, Xiao Y, Liu C, Xiao Q, Chen L, Zhu X, Xing X, Li Z, Zhang S, Zhang Z, Ma L, Wang E, Zhuang Z, Zheng Y, Chen W: CpG site-specific hypermethylation of p16INK4alpha in peripheral blood lymphocytes of PAH-exposed workers. Cancer Epidemiol Biomarkers Prev. 2012, 21: 182-190. 10.1158/1055-9965.EPI-11-0784.PubMed

74.

Woenckhaus M, Klein-Hitpass L, Grepmeier U, Merk J, Pfeifer M, Wild P, Bettstetter M, Wuensch P, Blaszyk H, Hartmann A, Hofstaedter F, Dietmaier W: Smoking and cancer-related gene expression in bronchial epithelium and non-small-cell lung cancers. J Pathol. 2006, 210: 192-204. 10.1002/path.2039.PubMed

75.

Boelens MC, van den Berg A, Fehrmann RS, Geerlings M, de Jong WK, te Meerman GJ, Sietsma H, Timens W, Postma DS, Groen HJ: Current smoking-specific gene expression signature in normal bronchial epithelium is enhanced in squamous cell lung cancer. J Pathol. 2009, 218: 182-191. 10.1002/path.2520.PubMed

76.

Spira A, Beane JE, Shah V, Steiling K, Liu G, Schembri F, Gilman S, Dumas YM, Calner P, Sebastiani P, Sridhar S, Beamis J, Lamb C, Anderson T, Gerry N, Keane J, Lenburg ME, Brody JS: Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer. Nat Med. 2007, 13: 361-366. 10.1038/nm1556.PubMed

77.

Beane J, Sebastiani P, Whitfield TH, Steiling K, Dumas YM, Lenburg ME, Spira A: A prediction model for lung cancer diagnosis that integrates genomic and clinical features. Cancer Prev Res (Phila). 2008, 1: 56-64. 10.1158/1940-6207.CAPR-08-0011.

78.

Blomquist T, Crawford EL, Mullins D, Yoon Y, Hernandez DA, Khuder S, Ruppel PL, Peters E, Oldfield DJ, Austermiller B, Anders JC, Willey JC: Pattern of antioxidant and DNA repair gene expression in normal airway epithelium associated with lung cancer diagnosis. Cancer Res. 2009, 69: 8629-8635. 10.1158/0008-5472.CAN-09-1568.PubMedPubMedCentral

79.

Gustafson AM, Soldi R, Anderlind C, Scholand MB, Qian J, Zhang X, Cooper K, Walker D, McWilliams A, Liu G, Szabo E, Brody J, Massion PP, Lenburg ME, Lam S, Bild AH, Spira A: Airway PI3K pathway activation is an early and reversible event in lung cancer development. Sci Transl Med. 2010, 2: 26ra25-10.1126/scitranslmed.3000251.PubMedPubMedCentral

80.

Wang X, Chorley BN, Pittman GS, Kleeberger SR, Brothers J, Liu G, Spira A, Bell DA: Genetic variation and antioxidant response gene expression in the bronchial airway epithelium of smokers at risk for lung cancer. PLoS One. 2010, 5: e11934-10.1371/journal.pone.0011934.PubMedPubMedCentral

81.

Beane J, Vick J, Schembri F, Anderlind C, Gower A, Campbell J, Luo L, Zhang XH, Xiao J, Alekseyev YO, Wang S, Levy S, Massion PP, Lenburg M, Spira A: Characterizing the impact of smoking and lung cancer on the airway transcriptome using RNA-Seq. Cancer Prev Res (Phila). 2011, 4: 803-817. 10.1158/1940-6207.CAPR-11-0212.

82.

Boyle JO, Gümüs ZH, Kacker A, Choksi VL, Bocker JM, Zhou XK, Yantiss RK, Hughes DB, Du B, Judson BL, Subbaramaiah K, Dannenberg AJ: Effects of cigarette smoke on the human oral mucosal transcriptome. Cancer Prev Res (Phila). 2010, 3: 266-278. 10.1158/1940-6207.CAPR-09-0192.

83.

Sridhar S, Schembri F, Zeskind J, Shah V, Gustafson AM, Steiling K, Liu G, Dumas YM, Zhang X, Brody JS, Lenburg ME, Spira A: Smoking-induced gene expression changes in the bronchial airway are reflected in nasal and buccal epithelium. BMC Genomics. 2008, 9: 259-10.1186/1471-2164-9-259.PubMedPubMedCentral

84.

Zhang X, Sebastiani P, Liu G, Schembri F, Zhang X, Dumas YM, Langer EM, Alekseyev Y, O’Connor GT, Brooks DR, Lenburg ME, Spira A: Similarities and differences between smoking-related gene expression in nasal and bronchial epithelium. Physiol Genomics. 2010, 41: 1-8. 10.1152/physiolgenomics.00167.2009.PubMed

85.

Zhang L, Xiao H, Zhou H, Santiago S, Lee JM, Garon EB, Yang J, Brinkmann O, Yan X, Akin D, Chia D, Elashoff D, Park NH, Wong DT: Development of transcriptomic biomarker signature in human saliva to detect lung cancer. Cell Mol Life Sci. 2012, 69: 3341-3350. 10.1007/s00018-012-1027-0.PubMedPubMedCentral

86.

Showe MK, Vachani A, Kossenkov AV, Yousef M, Nichols C, Nikonova EV, Chang C, Kucharczuk J, Tran B, Wakeam E, Yie TA, Speicher D, Rom WN, Albelda S, Showe LC: Gene expression profiles in peripheral blood mononuclear cells can distinguish patients with non-small cell lung cancer from patients with nonmalignant lung disease. Cancer Res. 2009, 69: 9202-9210. 10.1158/0008-5472.CAN-09-1378.PubMedPubMedCentral

87.

Rotunno M, Hu N, Su H, Wang C, Goldstein AM, Bergen AW, Consonni D, Pesatori AC, Bertazzi PA, Wacholder S, Shih J, Caporaso NE, Taylor PR, Landi MT: A gene expression signature from peripheral whole blood for stage I lung adenocarcinoma. Cancer Prev Res (Phila). 2011, 4: 1599-1608. 10.1158/1940-6207.CAPR-10-0170.

88.

Zander T, Hofmann A, Staratschek-Jox A, Classen S, Debey-Pascher S, Maisel D, Ansén S, Hahn M, Beyer M, Thomas RK, Gathof B, Mauch C, Delank KS, Engel-Riedel W, Wichmann HE, Stoelben E, Schultze JL, Wolf J: Blood-based gene expression signatures in non-small cell lung cancer. Clin Cancer Res. 2011, 17: 3360-3367. 10.1158/1078-0432.CCR-10-0533.PubMed

89.

Kato M, Slack FJ: microRNAs: small molecules with big roles - C. elegans to human cancer. Biol Cell. 2008, 100: 71-81. 10.1042/BC20070078.PubMed

90.

Eszlinger M, Krohn K, Hauptmann S, Dralle H, Giordano TJ, Paschke R: Perspectives for improved and more accurate classification of thyroid epithelial tumors. J Clin Endocrinol Metab. 2008, 93: 3286-3294. 10.1210/jc.2008-0201.PubMed

91.

Mascaux C, Laes JF, Anthoine G, Haller A, Ninane V, Burny A, Sculier JP: Evolution of microRNA expression during human bronchial squamous carcinogenesis. Eur Respir J. 2009, 33: 352-359.PubMed

92.

Xie Y, Todd NW, Liu Z, Zhan M, Fang H, Peng H, Alattar M, Deepak J, Stass SA, Jiang F: Altered miRNA expression in sputum for diagnosis of non-small cell lung cancer. Lung Cancer. 2010, 67: 170-176. 10.1016/j.lungcan.2009.04.004.PubMed

93.

Xing L, Todd NW, Yu L, Fang H, Jiang F: Early detection of squamous cell lung cancer in sputum by a panel of microRNA markers. Mod Pathol. 2010, 23: 1157-1164. 10.1038/modpathol.2010.111.PubMed

94.

Yu L, Todd NW, Xing L, Xie Y, Zhang H, Liu Z, Fang H, Zhang J, Katz RL, Jiang F: Early detection of lung adenocarcinoma in sputum by a panel of microRNA markers. Int J Cancer. 2010, 127: 2870-2878. 10.1002/ijc.25289.PubMedPubMedCentral

95.

Patnaik SK, Yendamuri S, Kannisto E, Kucharczuk JC, Singhal S, Vachani A: MicroRNA expression profiles of whole blood in lung adenocarcinoma. PLoS One. 2012, 7: e46045-10.1371/journal.pone.0046045.PubMedPubMedCentral

96.

Keller A, Backes C, Leidinger P, Kefer N, Boisguerin V, Barbacioru C, Vogel B, Matzas M, Huwer H, Katus HA, Stähler C, Meder B, Meese E: Next-generation sequencing identifies novel microRNAs in peripheral blood of lung cancer patients. Mol Biosyst. 2011, 7: 3187-3199. 10.1039/c1mb05353a.PubMed

97.

Jeong HC, Kim EK, Lee JH, Lee JM, Yoo HN, Kim JK: Aberrant expression of let-7a miRNA in the blood of non-small cell lung cancer patients. Mol Med Report. 2011, 4: 383-387.

98.

Leidinger P, Keller A, Borries A, Huwer H, Rohling M, Huebers J, Lenhof HP, Meese E: Specific peripheral miRNA profiles for distinguishing lung cancer from COPD. Lung Cancer. 2011, 74: 41-47. 10.1016/j.lungcan.2011.02.003.PubMed

99.

Keller A, Leidinger P, Borries A, Wendschlag A, Wucherpfennig F, Scheffler M, Huwer H, Lenhof HP, Meese E: miRNAs in lung cancer - studying complex fingerprints in patient's blood cells by microarray experiments. BMC Cancer. 2009, 9: 353-10.1186/1471-2407-9-353.PubMedPubMedCentral

100.

Hennessey PT, Sanford T, Choudhary A, Mydlarz WW, Brown D, Adai AT, Ochs MF, Ahrendt SA, Mambo E, Califano JA: Serum microRNA biomarkers for detection of non-small cell lung cancer. PLoS One. 2012, 7: e32307-10.1371/journal.pone.0032307.PubMedPubMedCentral

101.

Bianchi F, Nicassio F, Marzi M, Belloni E, Dall’olio V, Bernard L, Pelosi G, Maisonneuve P, Veronesi G, Di Fiore PP: A serum circulating miRNA diagnostic test to identify asymptomatic high-risk individuals with early stage lung cancer. EMBO Mol Med. 2011, 3: 495-503. 10.1002/emmm.201100154.PubMedPubMedCentral

102.

Keller A, Leidinger P, Gislefoss R, Haugen A, Langseth H, Staehler P, Lenhof HP, Meese E: Stable serum miRNA profiles as potential tool for non-invasive lung cancer diagnosis. RNA Biol. 2011, 8: 506-516. 10.4161/rna.8.3.14994.PubMed

103.

Chen X, Hu Z, Wang W, Ba Y, Ma L, Zhang C, Wang C, Ren Z, Zhao Y, Wu S, Zhuang R, Zhang Y, Hu H, Liu C, Xu L, Wang J, Shen H, Zhang J, Zen K, Zhang CY: 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. 10.1002/ijc.26177.PubMed

104.

Roth C, Kasimir-Bauer S, Pantel K, Schwarzenbach H: Screening for circulating nucleic acids and caspase activity in the peripheral blood as potential diagnostic tools in lung cancer. Mol Oncol. 2011, 5: 281-291. 10.1016/j.molonc.2011.02.002.PubMed

105.

Foss KM, Sima C, Ugolini D, Neri M, Allen KE, Weiss GJ: miR-1254 and miR-574-5p: serum-based microRNA biomarkers for early-stage non-small cell lung cancer. J Thorac Oncol. 2011, 6: 482-488. 10.1097/JTO.0b013e318208c785.PubMed

106.

Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X, Li Q, Li X, Wang W, Zhang Y, Wang J, Jiang X, Xiang Y, Xu C, Zheng P, Zhang J, Li R, Zhang H, Shang X, Gong T, Ning G, Wang J, Zen K, Zhang J, Zhang CY: Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008, 18: 997-1006. 10.1038/cr.2008.282.PubMed

107.

Boeri M, Verri C, Conte D, Roz L, Modena P, Facchinetti F, Calabrò E, Croce CM, 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. 10.1073/pnas.1100048108.PubMedPubMedCentral

108.

Shen J, Todd NW, Zhang H, Yu L, Lingxiao X, Mei Y, Guarnera M, Liao J, Chou A, Lu CL, Jiang Z, Fang H, Katz RL, Jiang F: Plasma microRNAs as potential biomarkers for non-small-cell lung cancer. Lab Invest. 2011, 91: 579-587. 10.1038/labinvest.2010.194.PubMed

109.

Rabinowits G, Gercel-Taylor C, Day JM, Taylor DD, Kloecker GH: Exosomal microRNA: a diagnostic marker for lung cancer. Clin Lung Cancer. 2009, 10: 42-46. 10.3816/CLC.2009.n.006.PubMed

110.

Stroun M, Anker P, Lyautey J, Lederrey C, Maurice PA: Isolation and characterization of DNA from the plasma of cancer patients. Eur J Cancer Clin Oncol. 1987, 23: 707-712. 10.1016/0277-5379(87)90266-5.PubMed

111.

Fournié GJ, Courtin JP, Laval F, Chalé JJ, Pourrat JP, Pujazon MC, Lauque D, Carles P: Plasma DNA as a marker of cancerous cell death. Investigations in patients suffering from lung cancer and in nude mice bearing human tumours. Cancer Lett. 1995, 91: 221-227. 10.1016/0304-3835(95)03742-F.PubMed

112.

Sozzi G, Conte D, Mariani L, Lo Vullo S, Roz L, Lombardo C, Pierotti MA, Tavecchio L: Analysis of circulating tumor DNA in plasma at diagnosis and during follow-up of lung cancer patients. Cancer Res. 2001, 61: 4675-4678.PubMed

113.

Sozzi G, Conte D, Leon M, Ciricione R, Roz L, Ratcliffe C, Roz E, Cirenei N, Bellomi M, Pelosi G, Pierotti MA, Pastorino U: Quantification of free circulating DNA as a diagnostic marker in lung cancer. J Clin Oncol. 2003, 21: 3902-3908. 10.1200/JCO.2003.02.006.PubMed

114.

Xie GS, Hou AR, Li LY, Gao YN, Cheng SJ: Quantification of plasma DNA as a screening tool for lung cancer. Chin Med J (Engl). 2004, 117: 1485-1488.

115.

Sozzi G, Roz L, Conte D, Mariani L, Andriani F, Lo Vullo S, Verri C, Pastorino U: Plasma DNA quantification in lung cancer computed tomography screening: five-year results of a prospective study. Am J Respir Crit Care Med. 2009, 179: 69-74. 10.1164/rccm.200807-1068OC.PubMed

116.

Zhang R, Shao F, Wu X, Ying K: Value of quantitative analysis of circulating cell free DNA as a screening tool for lung cancer: a meta-analysis. Lung Cancer. 2010, 69: 225-231. 10.1016/j.lungcan.2009.11.009.PubMed

117.

Szpechcinski A, Dancewicz M, Kopinski P, Kowalewski J, Chorostowska-Wynimko J: Real-time PCR quantification of plasma DNA in non-small cell lung cancer patients and healthy controls. Eur J Med Res. 2009, 14: 237-240. 10.1186/2047-783X-14-S4-237.PubMedPubMedCentral

118.

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: 211-217. 10.1016/j.lungcan.2010.01.021.PubMed

119.

Yoon KA, Park S, Lee SH, Kim JH, Lee JS: Comparison of circulating plasma DNA levels between lung cancer patients and healthy controls. J Mol Diagn. 2009, 11: 182-185. 10.2353/jmoldx.2009.080098.PubMedPubMedCentral

120.

Paci M, Maramotti S, Bellesia E, Formisano D, Albertazzi L, Ricchetti T, Ferrari G, Annessi V, Lasagni D, Carbonelli C, De Franco S, Brini M, Sgarbi G, Lodi R: Circulating plasma DNA as diagnostic biomarker in non-small cell lung cancer. Lung Cancer. 2009, 64: 92-97. 10.1016/j.lungcan.2008.07.012.PubMed

121.

Akca H, Demiray A, Yaren A, Bir F, Koseler A, Iwakawa R, Bagci G, Yokota J: Utility of serum DNA and pyrosequencing for the detection of EGFR mutations in non-small cell lung cancer. Cancer Genet. 2013, 206: 73-80. 10.1016/j.cancergen.2013.01.005.PubMed

122.

Nakamura T, Sueoka-Aragane N, Iwanaga K, Sato A, Komiya K, Kobayashi N, Hayashi S, Hosomi T, Hirai M, Sueoka E, Kimura S: Application of a highly sensitive detection system for epidermal growth factor receptor mutations in plasma DNA. J Thorac Oncol. 2012, 7: 1369-1381. 10.1097/JTO.0b013e31825f2821.PubMed

123.

Isobe K, Hata Y, Kobayashi K, Hirota N, Sato K, Sano G, Sugino K, Sakamoto S, Takai Y, Shibuya K, Takagi K, Homma S: Clinical significance of circulating tumor cells and free DNA in non-small cell lung cancer. Anticancer Res. 2012, 32: 3339-3344.PubMed

124.

Dawson SJ, Tsui DW, Murtaza M, Biggs H, Rueda OM, Chin SF, Dunning MJ, Gale D, Forshew T, Mahler-Araujo B, Rajan S, Humphray S, Becq J, Halsall D, Wallis M, Bentley D, Caldas C, Rosenfeld N: Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Eng J Med. 2013, 368: 1199-1209. 10.1056/NEJMoa1213261.

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1741-7015/11/168/prepub

Title: Bridging the clinical gaps: genetic, epigenetic and transcriptomic biomarkers for the early detection of lung cancer in the post-National Lung Screening Trial era
Authors: John F Brothers
Kahkeshan Hijazi
Celine Mascaux
Randa A El-Zein
Margaret R Spitz
Avrum Spira
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: BMC Medicine / Issue 1/2013
Electronic ISSN: 1741-7015
DOI: https://doi.org/10.1186/1741-7015-11-168

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Bridging the clinical gaps: genetic, epigenetic and transcriptomic biomarkers for the early detection of lung cancer in the post-National Lung Screening Trial era

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

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