Relationship between tumor mutational burden, gene mutation status, and clinical characteristics in 340 cases of lung adenocarcinoma

Abstract

Tumor mutational burden (TMB) is an emerging predictive marker of response to immune checkpoint inhibitor therapies. We evaluated the correlation between clinical indicators and high‐throughput sequencing results and TMB in lung adenocarcinoma patients, with the aim of finding simpler and more economical factors as surrogate markers for TMB. The medical records, next‐generation sequencing data, and immunohistochemistry results of 340 lung adenocarcinoma patients who were admitted to the First Affiliated Hospital of Zhengzhou University between 2019 and 2020 were collected. The mutated genes were screened for, and the obtained mutated genes were subjected to functional enrichment analysis using R software. A protein–protein interaction (PPI) network was also constructed, and significant modules in the network were identified. Gene Ontology (GO) analyses were performed for the core genes. Univariate and multivariate correlation analyses were performed to judge the correlation between gene mutations and TMB. Genes with a junction mutation rate >1 were selected to construct PPI network and 13 high‐connection core genes were screened. The results of GO enrichment analysis showed that the biological processes related to mutant core genes mainly included mitotic cell cycle and cell aging. Subsequently, ATM (p = 0.006) and PIK3CA (p = 0.008) mutation positivity were identified by univariate and multivariate correlation analysis, while TP53 (p = 0.003) and EGFR (p = 0.008) mutation negativity were significantly associated with elevated TMB. The results of this study demonstrate that ATM‐ and PIK3CA‐positive and EGFR‐negative mutation status are strongly associated with high levels of TMB and have the potential to be predictive biomarkers of response to immune checkpoint inhibitors in lung adenocarcinoma patients.

Molecular mechanisms and prognostic value of the selenoprotein gene family in lung adenocarcinoma and lung squamous cell carcinoma

“…Particularly for advanced NSCLC, some drugs targeting EGFR, ALK, and ROS1 have been approved for clinical use and have achieved unexpected effects; some drugs targeting ERBB2, BRAF, MET, and RET are emerging and display great potential; and some drugs targeting other mutated genes are now in various stages of clinical trials and are expected in the next future [87][88][89]. More meaningfully, as the most commonly encountered alteration in NSCLC, particularly in LUAD, EGFR mutation was not only able to predict the response to EGFR tyrosine kinase inhibitors but could also evaluate postoperative recurrence and prognosis [90][91][92]. However, mutations in selenoprotein genes in NSCLC remain poorly understood.…”

A more novel and powerful prognostic gene signature of lung adenocarcinoma determined from the immune cell infiltration landscape

“…Recently, the tumor microenvironment (TME) has attracted much attention. Accumulating evidence suggests that a comprehensive understanding of the molecular composition of LUAD requires a focus not only on tumor cells but also on the TME ( 3 , 4 ). The TME is the environment surrounding the tumor, including surrounding blood vessels, immune cells, fibroblasts, signaling molecules, and the extracellular matrix ( 3 , 4 ).…”

“…Accumulating evidence suggests that a comprehensive understanding of the molecular composition of LUAD requires a focus not only on tumor cells but also on the TME ( 3 , 4 ). The TME is the environment surrounding the tumor, including surrounding blood vessels, immune cells, fibroblasts, signaling molecules, and the extracellular matrix ( 3 , 4 ). Tumors are closely related to the surrounding microenvironment and constantly interact with each other.…”

“…Tumors are closely related to the surrounding microenvironment and constantly interact with each other. The TME contains multiple cell populations, signaling factors, and structural molecules that interact with tumor cells and support various stages of tumorigenesis ( 3 , 4 ). Vast studies on TME have displayed that infiltrating immune cells play a key role in the development and progression of tumor and response to immunotherapy ( 5 , 6 ).…”