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PTPRO is a therapeutic target and correlated with immune infiltrates in pancreatic cancer.

ABSTRACT: As a member of protein tyrosine phosphatases (PTPs), the protein tyrosine phosphatase receptor type O (PTPRO) has attracted increasing attention for its important roles in cell signaling. Currently, the roles of PTPRO in human cancers remain elusive. Herein, we performed bioinformatic analyses and revealed the potential oncogenic role of PTPRO in specific cancer types. Further in vitro experiments indicated that inhibition of PTPRO suppresses the proliferative abilities of tumor cells in pancreatic cancer, blood cancer, and breast cancer. Moreover, small molecular PTPRO inhibitor could induce cell apoptosis and affect the cell cycle in pancreatic cancer. In addition, PTPRO expression promoted the infiltration of CD8+ T, macrophages, dendritic cells, and neutrophils, in pancreatic cancers. Our findings suggested PTPRO may serve as a potential drug target for pancreatic cancer.

SUBMITTER: Hou X

PROVIDER: S-EPMC8734421 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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PTPRO is a therapeutic target and correlated with immune infiltrates in pancreatic cancer.

Hou Xuben X Du Jintong J Fang Hao H

Journal of Cancer 20211030 24

As a member of protein tyrosine phosphatases (PTPs), the protein tyrosine phosphatase receptor type O (PTPRO) has attracted increasing attention for its important roles in cell signaling. Currently, the roles of PTPRO in human cancers remain elusive. Herein, we performed bioinformatic analyses and revealed the potential oncogenic role of PTPRO in specific cancer types. Further <i>in vitro</i> experiments indicated that inhibition of PTPRO suppresses the proliferative abilities of tumor cells in ...[more]

PMID: 35003364

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Project description:BackgroundPhospholipase A/acyltransferase (PLAAT) family exhibits O- and N-acyltransferase activity and biosynthesize N-acylated ethanolamine phospholipids. Previously, PLAAT4 was seen as a tumor suppressor, but the exact function of PLAAT4 in pancreatic cancer was still unknown. In this study, we investigated the relationship of PLAAT4 and pancreatic cancer.MethodsUsing the data from the cancer genome atlas (TCGA), Genotype-Tissue Expression (GTEx) database and Gene Expression Omnibus (GEO) datasets we compared the expression of PLAAT4 in normal and tumor tissues and analyzed the connections between PLAAT4 and several clinicopathological factors. Further, we conducted Gene ontology (GO) analysis, Gene set enrichment analysis (GSEA), single sample gene set enrichment analysis (ssGSEA) and estimate analysis to explore the association between PLAAT4 and biological function and immune infiltration. In addition, Kaplan-Meier (KM) analysis, univariate and multivariate Cox analysis were used to explore the association between PLAAT4 and prognosis. In addition, we plotted a nomogram according to the multivariate cox analysis visualizing the predictive ability of PLAAT4 on prognosis. In addition, we explore the influence of PLAAT4 on malignant behaviors of the pancreatic cancer cells in vitro.ResultsAfter comparing the expression of PLAAT4 in normal and tumor tissues, we found that the expression of PLAAT4 was significantly high in pancreatic ductal adenocarcinoma (PDAC) samples. In addition, the results of GO and GSEA found that the expression of PLAAT4 was related to cell cycle checkpoints, M phase, regulation by p53, cell cycle mitotic and etc. Further, ssGSEA has shown that PLAAT4 was positively related to the abundance of aDC, Th1 cells, Th2 cells and negatively related to the Th17 cells. Subsequently, KM analysis, univariate and multivariate Cox analysis were used to analyze the correlation between PLAAT4 and prognosis. Additionally, we found that higher expression of PLAAT4 was related to T stage, N stage, histologic grade, etc (P < 0.05) and has a significant correlation with poor Overall Survival (OS), Disease-Specific Survival (DSS) and Progression-Free Interval (PFI). At last, we proved that PLAAT4 contributed to the malignant behaviors of the pancreatic cancer cells.ConclusionThis study indicated PLAAT4 as a novel prognostic biomarker and an important molecular that mediated immune response in pancreatic cancer.

Dataset Information

PTPRO is a therapeutic target and correlated with immune infiltrates in pancreatic cancer.

Publications

PTPRO is a therapeutic target and correlated with immune infiltrates in pancreatic cancer.

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