Prognostic value of TP53 co-mutation status combined with EGFR mutation in patients with lung adenocarcinoma
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ORIGINAL ARTICLE – CANCER RESEARCH
Prognostic value of TP53 co‑mutation status combined with EGFR mutation in patients with lung adenocarcinoma Feng Wang1 · Ning Zhao1 · Ge Gao2 · Hong‑Bin Deng3 · Zhi‑Hui Wang1 · Li‑Li Deng1 · Yu Yang1 · Changlian Lu4 Received: 11 May 2020 / Accepted: 24 July 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Purpose TP53/EGFR co-mutation has been reported to affect the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in lung adenocarcinoma (LUAD). However, its impact on survival is unclear. In this analysis, we explored the prognostic effect of TP53/EGFR co-mutation in LUAD. Methods Clinical data and transcriptome sequencing of LUAD patients with matched genomic data were downloaded from the Cancer Genome Atlas (TCGA) database for overall survival (OS) analysis. Differential expression genes (DEGs) were recognized by R software and bioconductor package. Clusterprofiler was used for functional analysis. STRING was used for estimating PPI information and plug-in CytoHubba to screen hub modules in Cytoscape. The association between tumor mutation burden (TMB) and survival was also analyzed. Results OS was shorter for patients carrying TP53 mutation (MUT) than that of wild type (WT) (37.7 m vs 52.8 m; p = 0.040, HR = 1.38, 95% CI 1.01–1.89). Dual TP53/EGFR-MUT was associated with inferior OS compared with the dual WT/WT cohort (38.4 m vs 51.9 m; p = 0.023, HR 1.83, 95% CI 0.95–3.52). 316 DEGs between dual TP53/EGFR-MUT and dual WT/WT samples were obtained and functional analysis made known that DEGs were strikingly enriched in regulating the metabolism of important amino acids, cell division, cell cycle regulation, cell adhesion, and extracellular matrix composition. KEGG analysis discovered that DEGs were mainly enriched in signaling pathways such as PI3K-Akt, cytokine–cytokine receptor interaction, focal adhesions, and extracellular matrix receptor interaction. PPI network suggested that GPC3, CCL28, GPR37, and NPY genes were up-regulated in dual mutation samples. OS in the high TMB cohort was significantly better than that in the low TMB in patients with TP53 MUT(43.2 m vs 32.4 m; P = 0.007, HR = 0.52, 95% CI: 0.34-0.81), as well as in the combination of TP53 MUT and EGFR WT group (44.4 m vs 31.2 m; P = 0.021, HR = 0.55, 95% CI 0.34 − 0.89). Conclusions TP53 MUT is a poor prognostic factor in LUAD patients, and the prognosis of TP53/EGFR co-mutation is worse. GPC3, CCL28, GPR37, and NPY may be novel prognostic markers and potential therapeutic targets for patients with dual TP53/EGFR mutation LUAD. Keywords LUAD · EGFR · TP53 · Co-mutation · SNPs · TMB
Feng Wang, Ning Zhao, and Ge Gao have contributed equally to this work and can be considered co-first authors. * Li‑Li Deng [email protected] * Yu Yang [email protected] * Changlian Lu [email protected] 1
Department of Oncology, the Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, 150086 Harbin, Heilongjiang, People’
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