Identification of Genes Associated with Lung Adenocarcinoma Prognosis

Author(s): Zhe-Hao He, Wang Lv, Lu-Ming Wang, Yi-Qing Wang, Jian Hu*.

Journal Name: Combinatorial Chemistry & High Throughput Screening
Accelerated Technologies for Biotechnology, Bioassays, Medicinal Chemistry and Natural Products Research

Volume 22 , Issue 4 , 2019

Become EABM
Become Reviewer

Abstract:

Objective: Lung cancer is the most prevalent cancer in the world, and lung adenocarcinoma is the most common lung cancer subtype. Identification and determination of relevant prognostic markers are the key steps to personalized cancer management.

Methods: We collected the gene expression profiles from 265 tumor tissues of stage I patients from The Cancer Genome Atlas (TCGA) databases. Using Cox regression model, we evaluated the association between gene expression and the overall survival time of patients adjusting for gender and age at initial pathologic diagnosis.

Results: Age at initial pathologic diagnosis was identified to be associated with the survival, while gender was not. We identified that 15 genes were significantly associated with overall survival time of patients (FDR < 0.1). The 15-mRNA signature- based risk score was helpful to distinguish patients of high-risk group from patients of low-risk group.

Conclusion: Our findings reveal novel genes associated with lung adenocarcinoma survival and extend our understanding of how gene expression contributes to lung adenocarcinoma survival. These results are helpful for the prediction of the prognosis and personalized cancer management.

Keywords: Lung adenocarcinoma, gene, prognosis, cancer management, lung cancer, markers.

[1]
Ettinger, D.S.; Akerley, W.; Borghaei, H.; Chang, A.C.; Cheney, R.T.; Chirieac, L.R.; D’Amico, T.A.; Demmy, T.L.; Govindan, R.; Grannis, F.W., Jr; Grant, S.C.; Horn, L.; Jahan, T.M.; Komaki, R.; Kong, F.M.; Kris, M.G.; Krug, L.M.; Lackner, R.P.; Lennes, I.T.; Loo, B.W., Jr; Martins, R.; Otterson, G.A.; Patel, J.D.; Pinder-Schenck, M.C.; Pisters, K.M.; Reckamp, K.; Riely, G.J.; Rohren, E.; Shapiro, T.A.; Swanson, S.J.; Tauer, K.; Wood, D.E.; Yang, S.C.; Gregory, K.; Hughes, M. National comprehensive cancer network. Non-small cell lung cancer, version 2.2013. J. Natl. Compr. Canc. Netw., 2013, 11(6), 645-653. ; quiz 653.
[2]
Siegel, R.; Naishadham, D.; Jemal, A. Cancer statistics, 2013. CA Cancer J. Clin., 2013, 63(1), 11-30.
[3]
Williams, D.E.; Pairolero, P.C.; Davis, C.S.; Bernatz, P.E.; Payne, W.S.; Taylor, W.F.; Uhlenhopp, M.A.; Fontana, R.S. Survival of patients surgically treated for stage I lung cancer. J. Thorac. Cardiovasc. Surg., 1981, 82(1), 70-76.
[4]
Hu, Z.; Chen, X.; Zhao, Y.; Tian, T.; Jin, G.; Shu, Y.; Chen, Y.; Xu, L.; Zen, K.; Zhang, C.; Shen, H. Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. J. Clin. Oncol., 2010, 28(10), 1721-1726.
[5]
Ludwig, J.A.; Weinstein, J.N. Biomarkers in cancer staging, prognosis and treatment selection. Nat. Rev. Cancer, 2005, 5(11), 845-856.
[6]
Massuti, B.; Sanchez, J.M.; Hernando-Trancho, F.; Karachaliou, N.; Rosell, R. Are we ready to use biomarkers for staging, prognosis and treatment selection in early-stage non-small-cell lung cancer? Transl. Lung Cancer Res., 2013, 2(3), 208-221.
[7]
Gregg, S.Q.; Robinson, A.R.; Niedernhofer, L.J. Physiological consequences of defects in ERCC1-XPF DNA repair endonuclease. DNA Repair (Amst.), 2011, 10(7), 781-791.
[8]
Li, C.; Liu, M.; Yan, A.; Liu, W.; Hou, J.; Cai, L.; Dong, X. ERCC1 and the efficacy of cisplatin in patients with resected non-small cell lung cancer. Tumour Biol., 2014, 35(12), 12707-12712.
[9]
Wang, B.; Hurov, K.; Hofmann, K.; Elledge, S.J. NBA1, a new player in the Brca1 A complex, is required for DNA damage resistance and checkpoint control. Genes Dev., 2009, 23(6), 729-739.
[10]
Pavloff, N.; Rivard, D.; Masson, S.; Shen, S.H.; Mes-Masson, A.M. Sequence analysis of the large and small subunits of human ribonucleotide reductase. DNA Seq., 1992, 2(4), 227-234.
[11]
Reynolds, C.; Obasaju, C.; Schell, M.J.; Li, X.; Zheng, Z.; Boulware, D.; Caton, J.R.; Demarco, L.C.; O’Rourke, M.A.; Shaw Wright, G.; Boehm, K.A.; Asmar, L.; Bromund, J.; Peng, G.; Monberg, M.J.; Bepler, G. Randomized phase III trial of gemcitabine-based chemotherapy with in situ RRM1 and ERCC1 protein levels for response prediction in non-small-cell lung cancer. J. Clin. Oncol., 2009, 27(34), 5808-5815.
[12]
Rosell, R.; Danenberg, K.D.; Alberola, V.; Bepler, G.; Sanchez, J.J.; Camps, C.; Provencio, M.; Isla, D.; Taron, M.; Diz, P.; Artal, A. Spanish Lung Cancer Group.Ribonucleotide reductase messenger RNA expression and survival in gemcitabine/cisplatin-treated advanced non-small cell lung cancer patients. Clin. Cancer Res., 2004, 10(4), 1318-1325.
[13]
Boukovinas, I.; Papadaki, C.; Mendez, P.; Taron, M.; Mavroudis, D.; Koutsopoulos, A.; Sanchez-Ronco, M.; Sanchez, J.J.; Trypaki, M.; Staphopoulos, E.; Georgoulias, V.; Rosell, R.; Souglakos, J. Tumor BRCA1, RRM1 and RRM2 mRNA expression levels and clinical response to first-line gemcitabine plus docetaxel in non-small-cell lung cancer patients. PLoS One, 2008, 3(11), e3695.
[14]
Nelson, D.B.; Lapid, D.J.; Mitchell, K.G.; Correa, A.M.; Hofstetter, W.L.; Mehran, R.J.; Rice, D.C.; Sepesi, B.; Walsh, G.L.; Vaporciyan, A.A.; Swisher, S.G.; Roth, J.A.; Antonoff, M.B. Perioperative outcomes for stage I Non-small cell lung cancer: differences between men and women. Ann. Thorac. Surg., 2018, 106(5), 1499-1503.
[15]
Gray, R.J. Modeling survival data: Extending the Cox model. J. Am. Stat. Assoc., 2002, 97, 353-354.
[16]
Benjamini, Y.; Hochberg, Y. Controlling the false discovery rate: A practical and powerful approach to multiple testing. J. R. Stat. Soc. B, 1995, 57, 289-300.
[17]
Uramoto, H.; Sugio, K.; Oyama, T.; Nakata, S.; Ono, K.; Yoshimastu, T.; Morita, M.; Yasumoto, K. Expression of endoplasmic reticulum molecular chaperone Grp78 in human lung cancer and its clinical significance. Lung Cancer, 2005, 49(1), 55-62.
[18]
Keniry, M.; Pires, M.M.; Mense, S.; Lefebvre, C.; Gan, B.; Justiano, K.; Lau, Y.K.; Hopkins, B.; Hodakoski, C.; Koujak, S.; Toole, J.; Fenton, F.; Calahan, A.; Califano, A.; DePinho, R.A.; Maurer, M.; Parsons, R. Survival factor NFIL3 restricts FOXO-induced gene expression in cancer. Genes Dev., 2013, 27(8), 916-927.
[19]
Zhu, Z.; Zhang, F.; Hu, H.; Bakshi, A.; Robinson, M.R.; Powell, J.E.; Montgomery, G.W.; Goddard, M.E.; Wray, N.R.; Visscher, P.M.; Yang, J. Integration of summary data from GWAS and eQTL studies predicts complex trait gene targets. Nat. Genet., 2016, 48(5), 481-487.
[20]
Liao, Z.; Wang, X.; Lin, D.; Zou, Q. Construction and identification of the RNAi recombinant lentiviral vector targeting human DEPDC7 gene. Interdiscip. Sci., 2017, 9(3), 350-356.
[21]
D’Andrea, E.L.; Ferravante, A.; Scudiero, I.; Zotti, T.; Reale, C.; Pizzulo, M.; De La Motte, L.R.; De Maio, C.; Mazzone, P.; Telesio, G.; Vito, P.; Stilo, R. The Dishevelled, EGL-10 and pleckstrin (DEP) domain-containing protein DEPDC7 binds to CARMA2 and CARMA3 proteins, and regulates NF-κB activation. PLoS One, 2014, 9(12), e116062.
[22]
Walker, M.M.; Ellis, S.M.; Auza, M.J.; Patel, A.; Clark, P. The intercellular adhesion molecule, cadherin-10, is a marker for human prostate luminal epithelial cells that is not expressed in prostate cancer. Mod. Pathol., 2008, 21(2), 85-95.
[23]
Ahn, J.W.; Kim, H.S.; Yoon, J.K.; Jang, H.; Han, S.M.; Eun, S.; Shim, H.S.; Kim, H.J.; Kim, D.J.; Lee, J.G.; Lee, C.Y.; Bae, M.K.; Chung, K.Y.; Jung, J.Y.; Kim, E.Y.; Kim, S.K.; Chang, J.; Kim, H.R.; Kim, J.H.; Lee, M.G.; Cho, B.C.; Lee, J.H.; Bang, D. Identification of somatic mutations in EGFR/KRAS/ALK-negative lung adenocarcinoma in never-smokers. Genome Med., 2014, 6(2), 18.
[24]
Dhillon, A.S.; Tulchinsky, E. FRA-1 as a driver of tumour heterogeneity: A nexus between oncogenes and embryonic signalling pathways in cancer. Oncogene, 2015, 34(34), 4421-4428.
[25]
Pandyra, A.A.; Mullen, P.J.; Goard, C.A.; Ericson, E.; Sharma, P.; Kalkat, M.; Yu, R.; Pong, J.T.; Brown, K.R.; Hart, T.; Gebbia, M.; Lang, K.S.; Giaever, G.; Nislow, C.; Moffat, J.; Penn, L.Z. Genome-wide RNAi analysis reveals that simultaneous inhibition of specific mevalonate pathway genes potentiates tumor cell death. Oncotarget, 2015, 6(29), 26909-269021.
[26]
Guo, Y.; Zhang, X.; Yang, M.; Miao, X.; Shi, Y.; Yao, J.; Tan, W.; Sun, T.; Zhao, D.; Yu, D.; Liu, J.; Lin, D. Functional evaluation of missense variations in the human MAD1L1 and MAD2L1 genes and their impact on susceptibility to lung cancer. J. Med. Genet., 2010, 47(9), 616-622.
[27]
Li, D.; Meng, Q.; Zhang, H.; Feng, T.; Liu, M.; Cai, L. Mitotic arrest deficient-like 1 is correlated with poor prognosis in small-cell lung cancer after surgical resection. Tumour Biol., 2016, 37(4), 4393-4398.
[28]
Allerstorfer, S.; Sonvilla, G.; Fischer, H.; Spiegl-Kreinecker, S.; Gauglhofer, C.; Setinek, U.; Czech, T.; Marosi, C.; Buchroithner, J.; Pichler, J.; Silye, R.; Mohr, T.; Holzmann, K.; Grasl-Kraupp, B.; Marian, B.; Grusch, M.; Fischer, J.; Micksche, M.; Berger, W. FGF5 as an oncogenic factor in human glioblastoma multiforme: autocrine and paracrine activities. Oncogene, 2008, 27(30), 4180-4190.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 22
ISSUE: 4
Year: 2019
Page: [220 - 224]
Pages: 5
DOI: 10.2174/1386207322666190404152140
Price: $58

Article Metrics

PDF: 19
HTML: 2
PRC: 1

Special-new-year-discount