Dataset Information

Expression profiling of ubiquitin-related genes in LKB1 mutant lung adenocarcinoma.

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.

SUBMITTER: Wang G

PROVIDER: S-EPMC6125361 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Expression profiling of ubiquitin-related genes in LKB1 mutant lung adenocarcinoma.

Wang Guanghui G Bie Fenglong F Qu Xiao X Yang Xudong X Liu Shaorui S Wang Yu Y Huang Cuicui C Wang Kai K Du Jiajun J

Scientific reports 20180905 1

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 proport ...[more]

PMID: 30185829

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Project description:The purpose of this study was to explore platinum resistance-related biomarkers and mechanisms in lung adenocarcinoma. Through the analysis of gene expression data of lung adenocarcinoma patients and normal patients from The Cancer Genome Atlas, Gene Expression Omnibus database, and A database of genes related to platinum resistance, platinum resistance genes in lung adenocarcinoma and platinum resistance-related differentially expressed genes were obtained. After screening by a statistical significance threshold, a total of 252 genes were defined as platinum resistance genes with significant differential expression, of which 161 were up-regulated and 91 were down-regulated. The enrichment results of up-regulated gene Gene Ontology (GO) showed that TOP3 entries related to biological processes (BP) were double-strand break repair, DNA recombination, DNA replication, the down-regulated gene GO enriches the TOP3 items about biological processes (BP) as a response to lipopolysaccharide, muscle cell proliferation, response to molecule of bacterial origin. Gene Set Enrichment Analysis showed that the top three were e2f targets, g2m checkpoint, and rgf beta signaling. A prognostic model based on non-negative matrix factorization classification showed the characteristics of high- and low-risk groups. The prognostic model established by least absolute shrinkage and selection operator regression and risk factor analysis showed that genes such as HOXB7, NT5E, and KRT18 were positively correlated with risk score. By analyzing the differences in m6A regulatory factors between high- and low-risk groups, it was found that FTO, GPM6A, METTL3, and YTHDC2 were higher in the low-risk group, while HNRNPA2B1, HNRNPC, TGF2BP1, IGF2BP2, IGF2BP3, and RBM15B were higher in the high-risk group. Immune infiltration and drug sensitivity analysis also showed the gene characteristics of the platinum-resistant population in lung adenocarcinoma. ceRNA analysis showed that has-miR-374a-5p and RP6-24A23.7 were lower in the tumor expression group, and that the survival of the low expression group was worse than that of the high expression group. In conclusion, the results of this study show that platinum resistance-related differentially expressed genes in lung adenocarcinoma are mainly concentrated in biological processes such as DNA recombination and response to lipopolysaccharide. The validation set proved that the high-risk group of our prognostic model had poor survival. M6A regulatory factor analysis, immune infiltration, and drug sensitivity analysis all showed differences between high and low-risk groups. ceRNA analysis showed that has-miR-374a-5p and RP6-24A23.7 could be protective factors. Further exploration of the potential impact of these genes on the risk and prognosis of drug-resistant patients with lung adenocarcinoma would provide theoretical support for future research.

Dataset Information

Expression profiling of ubiquitin-related genes in LKB1 mutant lung adenocarcinoma.

Publications

Expression profiling of ubiquitin-related genes in LKB1 mutant lung adenocarcinoma.

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