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CD73 acts as a prognostic biomarker and promotes progression and immune escape in pancreatic cancer.

ABSTRACT: CD73 is a glycosylphosphatidylinositol (GPI)-anchored protein that attenuates tumour immunity via cooperating with CD39 to generate immunosuppressive adenosine. Therefore, CD73 blockade has been incorporated into clinical trials for cancers based on preclinical efficacy. However, the biological role and underlying mechanism of CD73 in pancreatic cancer (PC) microenvironment and its prognostic impact have not been comprehensively studied. In this article, we found that the expression of CD73 was up-regulated in PC tissues and patients with higher CD73 expression had poorer overall survival (OS) and disease-free survival (DFS) in multiple publicly available databases. Higher CD73 expression was significantly associated with its reduced methylation, and only the hypomethylation of CpG site at cg23172664 was obviously correlated with poorer OS. Then, Metascape analysis and GSEA showed that CD73 may play an important role in PC progression and immune regulations. Notably, CD73 was verified to be negatively correlated with infiltrating levels of CD8+ T cells and ??+ T cells in both TCGA and GEO cohorts via the CIBERSORT algorithm. In addition, patients with higher CD73 expression also tended to have higher PD-L1 expression and tumour mutation load. It seemed that CD73 might be a promising biomarker for the response to the anti-PD-1/PD-L1 treatment in PC. In conclusion, these results reveal that CD73 may function as a promotor in cancer progression and a regulator in immune patterns via CD73-related pathways. Blockade of CD73 might be a promising therapeutic strategy for PC.

SUBMITTER: Chen Q

PROVIDER: S-EPMC7412695 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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CD73 acts as a prognostic biomarker and promotes progression and immune escape in pancreatic cancer.

Chen Qiangda Q Pu Ning N Yin Hanlin H Zhang Jicheng J Zhao Guochao G Lou Wenhui W Wu Wenchuan W

Journal of cellular and molecular medicine 20200709 15

CD73 is a glycosylphosphatidylinositol (GPI)-anchored protein that attenuates tumour immunity via cooperating with CD39 to generate immunosuppressive adenosine. Therefore, CD73 blockade has been incorporated into clinical trials for cancers based on preclinical efficacy. However, the biological role and underlying mechanism of CD73 in pancreatic cancer (PC) microenvironment and its prognostic impact have not been comprehensively studied. In this article, we found that the expression of CD73 was ...[more]

PMID: 32643277

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Project description:BackgroundCopine1 (CPNE1), the first discovered CPNE1 family member, participates in the process of carcinogenesis and development of diverse tumors. Our study aimed to investigate the expression and prognostic value of CPNE1 gene in hepatocellular carcinoma (HCC), to explore its functional network in HCC and its effects on biological behaviors.MethodsHCCDB, CCLE, HPA and LinkedOmics online databases were used to explore the expression of CPNE1 gene and analyze the co-expression network of CPNE1 in hepatocellular carcinoma. Gene set enrichment analysis (GSEA) was used for GO functional annotation, KEGG pathway enrichment analysis and regulators of CPNE1 networks in LIHC. HepG2 and MHCC-97H cells were selected to construct CPNE1 knockdown cell lines by transfection with siRNA, and Hep3B cell was selected to construct CPNE1 overexpression cell line by transfection with plasmid. The effect of CPNE1 on the proliferation of hepatocellular carcinoma cells was examined by CCK8 assay and clone formation assay; the effect of CPNE1 on the migration ability of hepatocellular carcinoma cells was assessed by cell scratch assay and Transwell cell migration assay; finally, the expression of related signaling pathway proteins was examined by Western Blot. The correlation of CPNE1 expression with immune infiltration and immune checkpoint molecules in HCC tissues was analyzed using TIMER online database and GSEA.ResultsCPNE1 was highly expressed in HCC tissues and significantly correlated with sex, age, cancer stage and tumor grade. Overall survival (OS) was significantly lower in patients with high CPNE1 expression than in patients with low CPNE1 expression, and CPNE1 could be used as an independent prognostic indicator for HCC. Knockdown of CPNE1 gene inhibited the AKT/P53 pathway, resulting in decreased proliferation, migration and invasion of HCC cells. Overexpression of CPNE1 gene showed the opposite results. The level of CPNE1 expression in HCC was significantly and positively correlated with the level of infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells (P < 0.001). GSEA results also showed that CPNE1 of LIHC was involved in some immune response regulating signaling pathways.ConclusionsOur study firstly found the expression of CPNE1 was significantly higher in LIHC tissues than in normal liver tissues, and high CPNE1 expression was associated with poor prognosis. In addition, we identified the possible mechanism by which CPNE1 functioned in LIHC. CPNE1 influenced AKT/P53 pathway activation and LIHC cell proliferation and migration. There was a significant correlation between CPNE1 expression and tumor immune infiltration in LIHC.

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CD73 acts as a prognostic biomarker and promotes progression and immune escape in pancreatic cancer.

Publications

CD73 acts as a prognostic biomarker and promotes progression and immune escape in pancreatic cancer.

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