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SGEF is a potential prognostic and therapeutic target for lung adenocarcinoma.

ABSTRACT: BACKGROUND:SH3-containing guanine nucleotide exchange factor (SGEF), a RhoG-specific guanine nucleotide exchange factor (GEF), was consider as a key signal that determines cancer cell invasion. Although SGEF has been considered to highly express in glioma and prostate cancer. However, it is not well illustrated in LAC. METHODS:In this experiment, expression of SGEF was detected in 92 LAC and corresponding normal tissue samples by immunohistochemistry. In addition, we evaluated the invasion and migration of lung adenocarcinoma cells by the gain and loss of SGEF expression. Furthermore, RhoG activity was measured by GST pull-down assay. RESULTS:SGEF is highly expressed in LAC tissues than in normal lung tissues and was associated with the TNM stage. Lung adenocarcinoma patients with low SGEF subgroup had longer overall survival compared to those with high expression. Furthermore, univariate analysis showed that SGEF expression was an independent prognostic factor for overall survival in lung adenocarcinoma. Silencing of SGEF effectively suppressed the invasion and migration of human lung adenocarcinoma cells in vitro by inhibiting RhoG activity, and over-expression of SGEF could reverse this phenomena. CONCLUSION:SGEF is a novel prognostic target in human lung adenocarcinoma.

SUBMITTER: Chen Q

PROVIDER: S-EPMC5816374 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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SGEF is a potential prognostic and therapeutic target for lung adenocarcinoma.

Chen Qian Q Lu Xiao X Liu Quan-Xing QX Zhou Dong D Qiu Yuan Y Dai Ji-Gang JG Zheng Hong H

World journal of surgical oncology 20180217 1

<h4>Background</h4>SH3-containing guanine nucleotide exchange factor (SGEF), a RhoG-specific guanine nucleotide exchange factor (GEF), was consider as a key signal that determines cancer cell invasion. Although SGEF has been considered to highly express in glioma and prostate cancer. However, it is not well illustrated in LAC.<h4>Methods</h4>In this experiment, expression of SGEF was detected in 92 LAC and corresponding normal tissue samples by immunohistochemistry. In addition, we evaluated the ...[more]

PMID: 29454349

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Project description:BackgroundThe current study aimed to investigate the interrelation between P2RY14 and the prognosis of patients suffering from lung adenocarcinoma (LUAD) following surgery.MethodsThe differentially expressed gene (DEG) P2RY14 was screened by the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and Immunology Database and Analysis Portal (ImmPort) databases. The relationship between P2RY14 and clinical data of LUAD was analyzed in TCGA and Kaplan-Meier (KM)-plotter databases. The association of P2RY14 with immune cells and immune-related expressed genes was analyzed in the Tumor Immune Estimation Resource (TIMER) database. A retrospective analysis of the 100 patients clinical data undergoing pulmonary adenocarcinoma surgery admitted to Nanjing Chest Hospital. Immunohistochemistry (IHC) analysis was carried out to evaluate the P2RY14 expression in lung cancer tissues, and quantitative reverse transcription PCR (RT-qPCR) was used to confirm the mRNA expression of this gene in LUAD tissues. And their survival was evaluated. KM method and the log-rank test were used for univariate survival analysis, and the Cox regression method was employed for multivariate survival analysis.ResultsP2Y14 was the DEG identified by the database. P2Y14 expression was upregulated in para-cancer tissues in comparison to cancer tissues. Patients suffering from LUAD who have high P2RY14 expression had a better prognosis than those with low expression. P2RY14 expression was shown to be substantially linked with immune invasion in the TIMER database. Finally, the trial included 100 patients, of which 80 died and 20 survived with a mean overall survival (OS) of 48 months. Between the high and low expression groups of P2RY14, there were statistically significant variations in the clinical stage and differentiation degree (P<0.05). Cox regression analysis revealed that differentiation degree, smoking history, and P2RY14 expression were independent risk factors for the prognosis of LUAD patients (all P<0.05).ConclusionsP2RY14 can substantially prolong the OS of patients suffering from LUAD and can be utilized as a new LUAD predictive biomarker. P2RY14 may be related to LUAD immune invasion and have an essential role in inhibiting tumor cell immune escape within the LUAD microenvironment.

Project description:BackgroundGlucosamine-Phosphate N-Acetyltransferase 1 (GNPNAT1) is a critical enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine. It has many important functions, such as protein binding, monosaccharide binding, and embryonic development and growth. However, the role of GNPNAT1 in lung adenocarcinoma (LUAD) remains unclear.MethodsIn this study, we explored the expression pattern and prognostic value of GNPNAT1 in LUAD across TCGA and GEO databases and assessed its independent prognostic value via Cox analysis. LinkedOmics and GEPIA2 were applied to investigate coexpression and functional networks associated with GNPNAT1. The TIMER web tool was deployed to assess the correlation between GNPNAT1 and the main six types of tumor-infiltrating immune cells. Besides, the correlations between GNPNAT1 and the LUAD common genetic mutations, TMB, and immune signatures were examined.ResultsGNPNAT1 was validated upregulated in tumor tissues in TCGA-LUAD and GEO cohorts. Moreover, in both TCGA and GEO cohorts, high GNPNAT1 expression was found to be associated with poor overall survival. Cox analysis showed that high GNPNAT1 expression was an independent risk factor for LUAD. Functional network analysis suggested that GNPNAT1 regulates cell cycle, ribosome, proteasome, RNA transport, and spliceosome signaling through pathways involving multiple cancer-related kinases and E2F family. In addition, GNPNAT1 correlated with infiltrating levels of B cells, CD4+ T cells, and dendritic cells. B cells and dendritic cells could predict the outcome of LUAD, and B cells and CD4+ T cells were significant independent risk factors. The TMB and mutations of KRAS, EGFR, STK11, and TP53 were correlated with GNPNAT1. At last, the correlation analysis showed GNPNAT1 correlated with most of the immune signatures we performed.ConclusionOur findings showed that GNPNAT1 was correlated to the prognosis and immune infiltration of LUAD. In particular, the tight relationship between GNPNAT1 and B cell marker genes may be the epicenter of the immune response and one of the key factors affecting the prognosis. Our findings laid the foundation for further research on the immunomodulatory role of GNPNAT1 in LUAD.

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SGEF is a potential prognostic and therapeutic target for lung adenocarcinoma.

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SGEF is a potential prognostic and therapeutic target for lung adenocarcinoma.

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