Abstract
Liver kinase B1 (LKB1) is a tumor suppressor, and there is a very high proportion of LKB1 mutation in lung adenocarcinoma. The function of LKB1 is closely related to that of ubiquitin related genes. Our objective is to analyze the changes in ubiquitin-related genes in LKB1 mutant lung adenocarcinoma. We searched The Cancer Genome Atlas (TCGA) and obtained gene expression profiles from 230 lung adenocarcinoma patients, which were then analyzed using R software. Kaplan–Meier curves and Cox proportional hazards regression were applied to estimate survival. Real-time reverse transcription PCR was used to verify gene expression. Gene function was explored by gene set enrichment analysis. There were significantly expressed differences in the ubiquitin-related gene SH3RF1 between the LKB1 mutant and wild-type lung adenocarcinoma patients (p = 9.78013E-05). Patients with LKB1 mutation and high expression of SH3RF1 had a better prognosis than the low expression group (HR 0.356, 95% CI 0.136–0.929, p = 0.035). SH3RF1 can influence cell cycle, apoptosis, DNA replication and the p53 signaling pathway. SH3RF1 might have great clinical value act as a diagnostic biomarker and indicator to evaluate the prognosis of LKB1 mutant lung adenocarcinoma patients. This gene also can become a new treatment target for LKB1 mutant lung adenocarcinoma patients.
Highlights
Lung cancer is one of the most common cancers and remains the leading cause of cancer-related death worldwide, leading to over a million deaths each year[1]
Our study focused on lung adenocarcinoma patients with Liver kinase B1 (LKB1) mutation and aimed to explore new diagnostic biomarkers to predict the prognosis for these patients
The function of LKB1 is closely related to ubiquitin systems[18], and we considered that ubiquitin system-related genes might have changed when accompanied by the occurrence of LKB1 mutation
Summary
Lung cancer is one of the most common cancers and remains the leading cause of cancer-related death worldwide, leading to over a million deaths each year[1]. LKB1 mutation is commonly accompanied by changes in ubiquitination and deubiquitination genes[5]. A data analysis using The Cancer Genome Atlas (TCGA) revealed that there were many differentially expressed ubiquitination and deubiquitination-associated genes between the LKB1 mutant group and the wild-type group. Significant difference in expression was found in ubiquitin-related genes, including DCAF4, PML, TRAF3, PRKN, TRIM2, RAB40B, RNF187, SH3RF1, USP2 and etc. We performed survival analysis for each differentially expressed gene and found that there was a significant survival difference in the LKB1 mutant patient group for only 12 genes: USP2, CAP1, DCAF4, PML, PRKN, RAB40B, RNF168, RNF187, SH3RF1, TRAF3, TRIM2, and TRIML2. The SH3RF1 gene may become a new diagnostic biomarker and treatment target in adenocarcinoma patients with the LKB1 mutation
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