Identification of a costimulatory molecule-based signature to predict prognostic risk of pancreatic adenocarcinoma

Abstract

We aimed to investigate the prognostic value of costimulatory molecules in PAAD by generating a CMS. Gene expression data and clinical factors of PAAD patients were obtained from TCGA. The signature was constructed using the survival package progressive Cox risk proportional regression model. Analyses of CMS-related genes, pathways, immune cell infiltration, and somatic mutations were conducted. A five-gene-based CMS was developed, and the risk score for CMS could be an independent risk factor for PAAD patients. Patients were divided into high- and low-risk groups based on the median Y of the CMS model. Differential analysis revealed 341 DEGs between the groups, and KEGG analysis demonstrated that these positively related genes in the high-risk group were mainly involved in chemical synaptic transmission pathway modulation and trans-synaptic signaling pathway regulation. Immune cell infiltration analysis revealed that the high-risk patients had higher proportions of M1 macrophages and T+ CD4 cells, but a lower proportion of M2 macrophages than that of the low-risk group. Mutational analysis revealed that the high-risk group showed a higher proportion of somatic mutations compared with that of the low-risk group. A CMS was developed, and the risk score could be an independent risk factor for PAAD patients.

Keywords

• pancreatic adenocarcinoma
• costimulatory molecule
• prognosis
• immune cell infiltration
• somatic mutation