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Integrative analysis of genomic sequencing data reveals higher prevalence of LRP1B mutations in lung adenocarcinoma patients with COPD.

ABSTRACT: Both chronic Obstruction Pulmonary Disease (COPD) and lung cancer are leading causes of death globally. Although COPD and lung cancer coexist frequently, it is unknown whether lung cancer patients with COPD harbor distinct genomic characteristics compared to those without COPD. In this study, we retrospectively analyzed genomic sequencing data from 272 patients with lung adenocarcinoma (LUAD) and compared the genetic alterations in LUAD patients with and without COPD. Integrative analysis of whole-genome and exome sequencing data revealed that COPD and non-COPD groups showed high concordance in mutational burden and spectra. Notably, we also found that EGFR mutations were more prevalent in LUAD patients without COPD, whereas mutated LRP1B was more frequently observed in LUAD patients with COPD. In addition, multi-variable analysis with logistic regression demonstrated that mutation of LRP1B was a predictive marker for the presence of COPD in the patients with LUAD. Our analysis demonstrated for the first time the high concordance in genomic alterations between the tumors from LUAD patients with and without COPD. We also identified higher prevalence of LRP1B among the LUAD patients with COPD, which might help understand the underlying mechanisms which link COPD and lung cancer.

SUBMITTER: Xiao D

PROVIDER: S-EPMC5437030 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Integrative analysis of genomic sequencing data reveals higher prevalence of LRP1B mutations in lung adenocarcinoma patients with COPD.

Xiao Dakai D Li Fuqiang F Pan Hui H Liang Han H Wu Kui K He Jianxing J

Scientific reports 20170518 1

Both chronic Obstruction Pulmonary Disease (COPD) and lung cancer are leading causes of death globally. Although COPD and lung cancer coexist frequently, it is unknown whether lung cancer patients with COPD harbor distinct genomic characteristics compared to those without COPD. In this study, we retrospectively analyzed genomic sequencing data from 272 patients with lung adenocarcinoma (LUAD) and compared the genetic alterations in LUAD patients with and without COPD. Integrative analysis of who ...[more]

PMID: 28522810

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Project description:BackgroundThe TP53 tumor suppressor gene is one of the most mutated genes in lung adenocarcinoma (LUAD) and plays a vital role in regulating the occurrence and progression of cancer. We aimed to elucidate the association between TP53 mutations, response to immunotherapies and the prognosis of LUAD.MethodsGenomic, transcriptomic, and clinical data of LUAD were downloaded from The Cancer Genome Atlas (TCGA) dataset. Gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, gene set enrichment analysis (GSEA). Gene set variation analysis (GSVA) were performed to determine the differences in biological pathways. A merged protein-protein interaction (PPI) network was constructed and analyzed. MSIpred was used to analyze the correlation between the expression of the TP53 gene, tumor mutation burden (TMB) and tumor microsatellite instability (MSI). CIBERSORT was used to calculate the abundance of immune cells. Univariate and multivariate Cox regression analyses were used to determine the prognostic value of TP53 mutations in LUAD.ResultsTP53 was the most frequently mutated in LUAD, with a mutational frequency of 48%. GO and KEGG enrichment analysis, GSEA, and GSVA results showed a significant upregulation of several signaling pathways, including PI3K-AKT mTOR (P < 0.05), Notch (P < 0.05), E2F target (NES = 1.8, P < 0.05), and G2M checkpoint (NES = 1.7, P < 0.05). Moreover, we found a significant correlation between T cells, plasma cells, and TP53 mutations (R2 < 0.01, P = 0.040). Univariate and multivariate Cox regression analyses revealed that the survival prognosis of LUAD patients was related to TP53 mutations (Hazard Ratio (HR) = 0.72 [95% CI, 0.53 to 0.98], P < 0.05), cancer status (P < 0.05), and treatment outcomes (P < 0.05). Lastly, the Cox regression models showed that TP53 exhibited good power in predicting three- and five-year survival rates.ConclusionsTP53 may be an independent predictor of response to immunotherapy in LUAD, and patients with TP53 mutations have higher immunogenicity and immune cell infiltration.

Dataset Information

Integrative analysis of genomic sequencing data reveals higher prevalence of LRP1B mutations in lung adenocarcinoma patients with COPD.

Publications

Integrative analysis of genomic sequencing data reveals higher prevalence of LRP1B mutations in lung adenocarcinoma patients with COPD.

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