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Role of tumor mutation burden-related signatures in the prognosis and immune microenvironment of pancreatic ductal adenocarcinoma

Authors :
Rong Tang
Xiaomeng Liu
Wei Wang
Jie Hua
Jin Xu
Chen Liang
Qingcai Meng
Jiang Liu
Bo Zhang
Xianjun Yu
Si Shi
Source :
Cancer Cell International, Vol 21, Iss 1, Pp 1-14 (2021)
Publication Year :
2021
Publisher :
BMC, 2021.

Abstract

Abstract Background High tumor mutation burden (TMB) has gradually become a sensitive biomarker for predicting the response to immunotherapy in many cancers, including lung, bladder and head and neck cancers. However, whether high TMB predicts the response to immunotherapy and prognosis in pancreatic ductal adenocarcinoma (PDAC) remained obscure. Hence, it is significant to investigate the role of genes related to TMB (TRGs) in PDAC. Methods The transcriptome and mutation data of PDAC was downloaded from The Cancer Genome Atlas-Pancreatic Adenocarcinoma (TCGA). Five independent external datasets of PDAC were chosen to validate parts of our results. qRT-PCR and immunohistochemical staining were also performed to promote the reliability of this study. Results The median overall survival (OS) was significantly increased in TMB_low group compared with the counterpart with higher TMB score after tumor purity adjusted (P = 0.03). 718 differentially expressed TRGs were identified and functionally enriched in some oncogenic pathways. 67 TRGs were associated with OS in PDAC. A prognostic model for the OS was constructed and showed a high predictive accuracy (AUC = 0.849). We also found TMB score was associated with multiple immune components and signatures in tumor microenvironment. In addition, we identified a PDAC subgroup featured with TMBlowMicrosatellite instabilityhigh (MSIhigh) was associated with prolonged OS and a key molecule, ANKRD55, potentially mediating the survival benefits. Conclusion This study analyzed the biological function, prognosis value, implications for mutation landscape and potential influence on immune microenvironment of TRGs in PDAC, which contributed to get aware of the role of TMB in PDAC. Future studies are expected to investigate how these TRGs regulate the initiation, development or repression of PDAC.

Details

Language :
English
ISSN :
14752867
Volume :
21
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Cancer Cell International
Publication Type :
Academic Journal
Accession number :
edsdoj.4e68983c549a48c4b67e3caacf6e2219
Document Type :
article
Full Text :
https://doi.org/10.1186/s12935-021-01900-4