Identification of an Immune-Related Signature for Predicting Prognosis in Patients With Pancreatic Ductal Adenocarcinoma

Frontiers in Oncology

Bin Dong¹  Jianhui Wu¹  Liang Yan¹  Chunyi Hao¹  Xiuyun Tian²  Min Zhao³  Xiaoya Guan³  Weijia Wang³ 

[1] Institute, Beijing, China;;Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Central Laboratory, Peking University Cancer Hospital &;Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital &

关键词: immune-related genes;    immune signature;    pancreatic ductal adenocarcinoma;    prognosis;    tumor microenvironment;   

DOI  :  10.3389/fonc.2020.618215

来源: DOAJ

【 摘 要 】

PurposePancreatic ductal adenocarcinoma (PDAC) is one of the highest fatality rate cancers with poor survival rates. The tumor microenvironment (TME) is vital for tumor immune responses, leading to resistance to chemotherapy and poor prognosis of PDAC patients. This study aimed to provide a comprehensive evaluation of the immune genes and microenvironment in PDAC that might help in predicting prognosis and guiding clinical treatments.MethodsWe developed a prognosis-associated immune signature (i.e., PAIS) based on immune-associated genes to predict the overall survival of patients with PDAC. The clinical significance and immune landscapes of the signature were comprehensively analyzed.ResultsOwing to gene expression profiles from TCGA database, functional enrichment analysis revealed a significant difference in the immune response between PDAC and normal pancreas. Using transcriptome data analysis of a training set, we identified an immune signature represented by 5 genes (ESR2, IDO1, IL20RB, PPP3CA, and PLAU) related to the overall survival of patients with PDAC, significantly. This training set was well-validated in a test set. Our results indicated a clear association between a high-risk score and a very poor prognosis. Stratification analysis and multivariate Cox regression analysis revealed that PAIS was an important prognostic factor. We also found that the risk score was positively correlated with the inflammatory response, antigen-presenting process, and expression level of some immunosuppressive checkpoint molecules (e.g., CD73, PD-L1, CD80, and B7-H3). These results suggested that high-risk patients had a suppressed immune response. However, they could respond better to chemotherapy. In addition, PAIS was positively correlated with the infiltration of M2 macrophages in PDAC.ConclusionsThis study highlighted the relationship between the immune response and prognosis in PDAC and developed a clinically feasible signature that might serve as a powerful prognostic tool and help further optimize the cancer therapy paradigm.

【 授权许可】

Unknown