Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, Qiangda, Pu, Ning, Yin, Hanlin, Zhang, Jicheng, Zhao, Guochao, Lou, Wenhui, Wu, Wenchuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412695/
https://www.ncbi.nlm.nih.gov/pubmed/32643277
http://dx.doi.org/10.1111/jcmm.15500
_version_ 1783568663232643072
author Chen, Qiangda
Pu, Ning
Yin, Hanlin
Zhang, Jicheng
Zhao, Guochao
Lou, Wenhui
Wu, Wenchuan
author_facet Chen, Qiangda
Pu, Ning
Yin, Hanlin
Zhang, Jicheng
Zhao, Guochao
Lou, Wenhui
Wu, Wenchuan
author_sort Chen, Qiangda
collection PubMed
description 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 γδ(+) 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.
format Online
Article
Text
id pubmed-7412695
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-74126952020-08-10 CD73 acts as a prognostic biomarker and promotes progression and immune escape in pancreatic cancer Chen, Qiangda Pu, Ning Yin, Hanlin Zhang, Jicheng Zhao, Guochao Lou, Wenhui Wu, Wenchuan J Cell Mol Med Original Articles 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 γδ(+) 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. John Wiley and Sons Inc. 2020-07-09 2020-08 /pmc/articles/PMC7412695/ /pubmed/32643277 http://dx.doi.org/10.1111/jcmm.15500 Text en © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Chen, Qiangda
Pu, Ning
Yin, Hanlin
Zhang, Jicheng
Zhao, Guochao
Lou, Wenhui
Wu, Wenchuan
CD73 acts as a prognostic biomarker and promotes progression and immune escape in pancreatic cancer
title CD73 acts as a prognostic biomarker and promotes progression and immune escape in pancreatic cancer
title_full CD73 acts as a prognostic biomarker and promotes progression and immune escape in pancreatic cancer
title_fullStr CD73 acts as a prognostic biomarker and promotes progression and immune escape in pancreatic cancer
title_full_unstemmed CD73 acts as a prognostic biomarker and promotes progression and immune escape in pancreatic cancer
title_short CD73 acts as a prognostic biomarker and promotes progression and immune escape in pancreatic cancer
title_sort cd73 acts as a prognostic biomarker and promotes progression and immune escape in pancreatic cancer
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412695/
https://www.ncbi.nlm.nih.gov/pubmed/32643277
http://dx.doi.org/10.1111/jcmm.15500
work_keys_str_mv AT chenqiangda cd73actsasaprognosticbiomarkerandpromotesprogressionandimmuneescapeinpancreaticcancer
AT puning cd73actsasaprognosticbiomarkerandpromotesprogressionandimmuneescapeinpancreaticcancer
AT yinhanlin cd73actsasaprognosticbiomarkerandpromotesprogressionandimmuneescapeinpancreaticcancer
AT zhangjicheng cd73actsasaprognosticbiomarkerandpromotesprogressionandimmuneescapeinpancreaticcancer
AT zhaoguochao cd73actsasaprognosticbiomarkerandpromotesprogressionandimmuneescapeinpancreaticcancer
AT louwenhui cd73actsasaprognosticbiomarkerandpromotesprogressionandimmuneescapeinpancreaticcancer
AT wuwenchuan cd73actsasaprognosticbiomarkerandpromotesprogressionandimmuneescapeinpancreaticcancer