Identification of Mutations Related to Cisplatin-Resistance and Prognosis of Patients With Lung Adenocarcinoma

Frontiers in Pharmacology
Rui LiXin Chen

Abstract

Background: Lung adenocarcinoma (LUAD) is the most common histologic type of non-small cell lung cancer (NSCLC; approximately 60%), and platinum-based chemotherapy is the cornerstone of the treatment for patients with LUAD. However, a considerable number of patients experience tumor recurrence after developing cisplatin (cis-diamminedichloroplatinum(II) or CDDP) resistance. Therefore, it is particularly important to screen primary CDDP-resistant LUAD patient populations, which can maximize the clinical benefits for these patients. Methods: Data for 61 LUAD cell lines were downloaded from the Genomics of Drug Sensitivity in Cancer (GDSC) database to screen for mutations related to CDDP susceptibility, and we conducted whole-exome sequencing (WES) of tumors from 45 LUAD patients from Zhujiang Hospital of Southern Medical University. Subsequently, the clinical prognostic value of these mutations was verified by using The Cancer Genome Atlas (TCGA)-LUAD cohort and our cohort (n = 45). Results: Based on drug sensitivity data for the GDSC-LUAD cell lines and survival analysis of the cohorts TCGA-LUAD and Local-LUAD, we found only one gene (GREB1) with mutations related to decreased CDDP sensitivity as well as worse overall survival (...Continue Reading

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Methods Mentioned

BETA
RNA-seq

Software Mentioned

clusterProfiler R package
TCGAbiolinks
R
Complexheatmap
ggpubr R
GSVA R
ssGSEA
limma
clusterProfiler R
GSEA

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