Dataset Information

CD148 Serves as a Prognostic Marker of Gastric Cancer and Hinders Tumor Progression by Dephosphorylating EGFR.

ABSTRACT: CD148 is a member of the receptor-type protein tyrosine phosphatase family encoded by the PTPRJ gene and has controversial impacts on cancers. In this study, we investigated the clinical significance of CD148 in gastric cancer and the possible mechanisms. Suppressed CD148 expression indicated adverse pathological features and poor outcomes in gastric cancer patients. CD148 overexpression impeded tumor proliferation, motility, and invasiveness, while CD148 knock-down or knockout promoted the ability of gastric cancer cells to grow and metastasize in vitro and in vivo. Mechanistically, CD148 negatively regulated EGFR phosphorylation of multiple tyrosine residues, including Y1173, Y1068, and Y1092, and remarkably inhibited downstream PI3K/AKT and MEK/ERK pathways. In silico analysis revealed that gene deletions or missense/truncated mutations of PTPRJ gene rarely occurred in gastric cancers. Instead, a 3' UTR-specific methylation might regulate CD148 expression, and the potential regulators were TET2 and TET3. Collectively, our results suggest that CD148 is a convincing prognostic marker as well as a potential therapeutic target for gastric cancer.

SUBMITTER: Sun Y

PROVIDER: S-EPMC7065996 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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CD148 Serves as a Prognostic Marker of Gastric Cancer and Hinders Tumor Progression by Dephosphorylating EGFR.

Sun Yiting Y Li Song S Yu Wenbin W Chen Cheng C Liu Teng T Li Lanbo L Zhang Di D Zhao Zeyi Z Gao Jing J Wang Xiao X Shi Duanbo D Liu Lian L

Journal of Cancer 20200219 9

CD148 is a member of the receptor-type protein tyrosine phosphatase family encoded by the <i>PTPRJ</i> gene and has controversial impacts on cancers. In this study, we investigated the clinical significance of CD148 in gastric cancer and the possible mechanisms. Suppressed CD148 expression indicated adverse pathological features and poor outcomes in gastric cancer patients. CD148 overexpression impeded tumor proliferation, motility, and invasiveness, while CD148 knock-down or knockout promoted t ...[more]

PMID: 32201537

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Project description:BackgroundRGS protein family members have recently became new potentially promising therapeutic targets in many cancers. However, as a key member of RGS family, RGS16 has seldom been studied in glioma. The present study was designed to investigate the prognostic value and biological function of RGS16 based on large-scale databases and functional assays in vitro.MethodsHere, we performed comprehensive analysis for the expression characteristic of RGS16 in Chinese Glioma Genome Atlas (CGGA) microarray database with 301 patients and validated in The Cancer Genome Atlas (TCGA) microarray and RNA sequencing database. Student's t-test, one-way ANOVA test and long-rank test were used to assess differences between groups. Kaplan-Meier survival, univariate and multivariate Cox analysis and ROC curve were used to estimate the survival distributions. Biological implication of abnormal expression of RGS16 in glioma was also explored. Functional analysis of RGS16 was performed in several glioblastoma (GBM) cell lines. R language and SPSS were used for statistical analysis and graphical work.ResultsWe found that the expression of RGS16 was positively related to the grade of glioma. High level of RGS16 commonly gathered in glioma of mesenchymal subtype and wild-type IDH1. Moreover, higher expression level of RGS16 was found to be significantly correlated with poor prognosis. The univariate and multivariate Cox regression analysis and ROC curve showed that RGS16 was an independent prognostic factor for glioma patients. Gene ontology analysis, gene set enrichment analysis, and gene set variation analysis suggested that the overexpression of RGS16 tightly related to cell proliferation, migration, epithelial-mesenchymal transition (EMT), immune and inflammatory response of glioma. Knockdown of RGS16 in glioma cell lines also showed that RGS16 promoted the malignant progress of glioma cell lines.ConclusionsRGS16 plays an important role in glioma progression and serves as an independent prognostic factor, especially in GBM patients.

Dataset Information

CD148 Serves as a Prognostic Marker of Gastric Cancer and Hinders Tumor Progression by Dephosphorylating EGFR.

Publications

CD148 Serves as a Prognostic Marker of Gastric Cancer and Hinders Tumor Progression by Dephosphorylating EGFR.

Similar Datasets

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