Open Journal Systems

Identification of Driver Genes in Lung Squamous Cell Carcinoma and Lung Adenocarcinoma

VIEWS - 104 (Abstract) 33 (PDF)
Zhengtai Li, Fusheng Li, Huixue Tang, Xiao Ge, Lida Xu, Changyuan Yu


The non-small cell lung cancer (NSCLC), including lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD), accounts for a large proportion of lung cancer cases. However, the mechanisms of LUSC and LUAD are very different, especially the pathogenesis of LUSC remains unclear. At present, the research on the targeted therapeutic sites of LUAD has approached maturity and these targets are of clinical significance. However, effective therapeutic targets have not been identified in LUSC, and at present, the same targeted therapeutic strategy for LUAD is also applied in LUSC treatment. We used the data from The Cancer Genome Atlas program to analyze the driver genes of LUAD and LUSC by two types of algorithms, namely, the OncodriveCLUST and Multi-Dendrix. Our results showed that the driver genes of LUAD concentrates in the KRAS/epidermal growth factor receptor/TP53 pathways, while LUSC involves multiple pathways, including PIK3CA, NFE2L2, and TP53. The results showed that different carcinogenic mechanisms exist between these two types of NSCLC, implying that different therapeutic targets for LUSC deserve our attention. At the same time, the results of survival analysis proved that the driver genes identified using the two algorithms in combination may be more valid and reliable than those identified by solely using MutsigCV.


Driver genes, Non-small cell lung cancer, OncodriveCLUST algorithm, Multi-Dendrix algorithm

Full Text:



Siegel RL, Miller KD, Jemal A, 2018, Cancer Statistics, 2018. CA Cancer J Clin. 68(1):7–30.

Herbst RS, Morgensztern D, Boshoff C, 2018, The Biology and Management of Non-small Cell Lung Cancer. Nature, 553(7689):446–54. DOI: 10.1038/nature25183.

Lindeman NI, Cagle PT, Aisner DL, et al., 2018, Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. J Thorac Oncol, 13(3):323–58. DOI: 10.1097/ jto.0000000000000002.

Pao W, Wang TY, Riely GJ, et al., 2005, KRAS Mutations and Primary Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib. PLoS Med, 2(1):e17. DOI: 10.1371/ journal.pmed.0020017.

Ding L, Getz G, Wheeler DA, et al., 2008, Somatic Mutations Affect Key Pathways in Lung Adenocarcinoma. Nature, 455(7216):1069–75.

Jamal-Hanjani M, Wilson GA, McGranahan N, et al., 2017, Tracking the Evolution of Non-small-cell Lung Cancer. N Engl J Med, 376(22):2109–21.

Campbell JD, Alexandrov A, Kim J, et al., 2016, Distinct Patterns of Somatic Genome Alterations in Lung Adenocarcinomas and Squamous Cell Carcinomas. Nat Genet, 48(6):607–16.

Greenman C, Stephens P, Smith R, et al., 2007, Patterns of Somatic Mutation in Human Cancer Genomes. Nature, 6(9):153–8.

Zheng CH, Yang W, Chong YW, et al., 2016, Identification of Mutated Driver Pathways in Cancer Using a Multi-objective Optimization Model. Comput Biol Med, 72:22–9.

Buisson R, Langenbucher A, Bowen D, et al., 2019, Passenger Hotspot Mutations in Cancer Driven by APOBEC3A and Mesoscale Genomic Features. Science, 364(6447):1228. DOI: 10.1126/science.aaw2872.

Cancer Genome Atlas Research Network, 2014, Comprehensive Molecular Profiling of Lung Adenocarcinoma. Nature, 511(7511):543–50. DOI: 10.1038/nature13385.

Cancer Genome Atlas Research Network, 2012, Comprehensive Genomic Characterization of Squamous Cell Lung Cancers. Nature, 489(7417):519–25. DOI: 10.1038/nature11404.

Relli V, Trerotola M, Guerra E, et al., 2019, Abandoning the Notion of non-small Cell Lung Cancer. Trends Mol Med, 25(7):585–94. DOI: 10.1016/j.molmed.2019.04.012.

Gonzalez-Perez A, Lopez-Bigas N, 2012, Functional Impact Bias Reveals Cancer Drivers. Nucleic Acids Res, 40(21):e169. DOI: 10.1093/nar/gks743.

Mayakonda A, Lin DC, Assenov Y, et al., 2018, Maftools: Efficient and Comprehensive Analysis of Somatic Variants in Cancer. Genome Res, 28(11):1747-56. DOI: 10.1101/ gr.239244.118.

Vaske CJ, Benz SC, Sanborn JZ, et al., 2010, Inference of Patient-specific Pathway Activities from Multi-dimensional Cancer Genomics Data Using PARADIGM. Bioinformatics, 26(12):i237–45. DOI: 10.1093/bioinformatics/btq182.

Vandin F, Upfal E, Raphael BJ, 2012, De novo Discovery of Mutated Driver Pathways in Cancer. Genome Res, 22(2):375–85. DOI: 10.1101/gr.120477.111.

Leiserson MD, Blokh D, Sharan R, et al., 2013, Simultaneous Identification of Multiple Driver Pathways in Cancer. PLoS Comput Biol, 9(5):e1003054. DOI: 10.1371/ journal.pcbi.1003054.

Lawrence MS, Stojanov P, Polak P, et al., 2013, Mutational Heterogeneity in Cancer and the Search for New Cancer-associated Genes. Nature, 499(7457):214–8.

Ahmad D, 2017, Epidemiology Study on P53 (Rs1614984) C>T Mutation in Cigarette Smokers. Braz Arch Biol Technol, 60:e160438. DOI: 10.1590/1678-4324-2017160438.

Alexandrov LB, Nik-Zainal S, Wedge DC, et al., 2013, Signatures of Mutational Processes in Human Cancer. Nature, 500(7463):415–21.

Anju S, Manish B, Nobunao W, et al., 2010, Gain of Nrf2 Function in Non-small-cell Lung Cancer Cells Confers Radioresistance. Antioxid Redox Signal, 13(11):1627–37. DOI: 10.1089/ars.2010.3219.

Sanchez-Vega F, Mina M, Armenia J, et al., 2018, Oncogenic Signaling Pathways in the Cancer Genome Atlas. Cell, 173(2):321–37.

Singh A, Venkannagari S, Oh KH, et al., 2016, Small Molecule Inhibitor of NRF2 Selectively Intervenes Therapeutic Resistance in KEAP1-Deficient NSCLC Tumors. ACS Chem Biol, 11(11):3214–25. DOI: 10.1021/ acschembio.6b00651.



  • There are currently no refbacks.

Copyright (c) 2019 Li, et al.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Recent Articles | About Journal | For Author | Fees | About Whioce

Copyright © Whioce Publishing Pte Ltd. All Rights Reserved.