Exome-Wide Association Study Identifies Low-Frequency Coding Variants in 2p23.2 and 7p11.2 Associated with Survival of Non–Small Cell Lung Cancer Patients

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Exome-Wide Association Study Identifies Low-Frequency Coding Variants in 2p23.2 and 7p11.2 Associated with Survival of Non–Small Cell Lung Cancer Patients Meng Zhu, PhD, Liguo Geng, MD, Wei Shen, PhD, Yuzhuo Wang, PhD, Jia Liu, MD, Yang Cheng, MD, Cheng Wang, PhD, Juncheng Dai, PhD, Guangfu Jin, PhD, Zhibin Hu, PhD, Hongxia Ma, PhD, Hongbing Shen, PhD Journal of Thoracic Oncology Volume 12, Issue 4, Pages 644-656 (April 2017) DOI: 10.1016/j.jtho.2016.12.025 Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 Summary of the study design and work flow. GWAS, genome-wide association studies; TCGA, The Cancer Genome Atlas; PLB1, phospholipase B1 gene; HR, hazard ratio; CCT6A, chaperonin containing TCP1 subunit 6A gene. Journal of Thoracic Oncology 2017 12, 644-656DOI: (10.1016/j.jtho.2016.12.025) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 2 Kaplan-Meier survival curves of patients with lung cancer in our data and The Cancer Genome Atlas. Individuals with AG/GG of rs33922584 (A) and GA of rs117512489 (B) exhibited a shorter survival time in our database. The association of rs33922584 was also validated by the imputation data of The Cancer Genome Atlas (C). Expression of chaperonin containing TCP1 subunit 6A gene (CCT6A) was significantly higher in individuals with AG of rs33922584 than in those with AA (D). Journal of Thoracic Oncology 2017 12, 644-656DOI: (10.1016/j.jtho.2016.12.025) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 3 Circos plots integrating the single-nucleotide polymorphisms (SNPs), gene-based analysis, and the five most significant pathways. Individual SNP and gene-based analysis p values for our exome chip data are shown as scatterplots on ideograms (A and B); p values of gene expression and survival in The Cancer Genome Atlas (TCGA) are shown on ideograms (C); –log10 of the individual SNP and the gene p values increase radially outward. The 32 labeled genes are significantly in both our gene-based analysis and the gene expression analysis of the TCGA (p < 0.05); The five most significant pathways identified in our data set and validated by the TCGA are shown as heatmaps on ideograms 1 to 5: (1) FIRESTEIN_CTNNB1_PATHWAY pathway; (2) WHITFIELD_CELL_CYCLE_G2_M pathway; (3) ZHANG_ANTIVIRAL_RESPONSE_TO_RIBAVIRIN_UP pathway; (4) DACOSTA_ERCC3_ALLELE_XPCS_VS_TTD_UP pathway; (5) SWEET_KRAS_TARGETS_UP pathway. These five pathways were derived from the Gene Set Enrichment Analysis (GSEA) database (http://software.broadinstitute.org/gsea/msigdb/index.jsp). Journal of Thoracic Oncology 2017 12, 644-656DOI: (10.1016/j.jtho.2016.12.025) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions