Identification of a Five-Gene Prognostic Signature Related to B Cells Infiltration in Pancreatic Adenocarcinoma

Int J Gen Med. 2021 Aug 30:14:5051-5068. doi: 10.2147/IJGM.S324432. eCollection 2021.

Abstract

Background: Pancreatic adenocarcinoma (PAAD) is an extremely malignant cancer. Immunotherapy is a promising avenue to increase the survival time of patients with PAAD.

Methods: RNA sequencing and clinical data for PAAD were downloaded from the TCGA database. The ssGSEA method and weighted gene co-expression network analysis were used to calculate the relative abundance of tumor-infiltrating immune cells and identify the related modules. Least absolute shrinkage and selection operator (LASSO) and Cox regression analyses were used to construct a prognostic model. MCPcounter and EPIC were also used to assess immune cell components using gene expression profiles.

Results: The B cells closely related module was identified, and five genes, including ARID5A, CLEC2B, MICAL1, MZB1, and RAPGEF1, were ultimately selected to establish a prognostic signature to calculate the risk scores of PAAD patients. Kaplan-Meier curves showed worse survival in the high-risk patients (p < 0.05), and the area under the receiver operating characteristic (ROC) curves of risk score for 1-year and 3-year survival were 0.78 and 0.80, respectively, based on the training set. Similar results were verified using the validated and combined sets. Interestingly, the low-risk group presented significantly elevated immune and stromal scores, proportion of B cells, and associations between these five genes and B cells were identified using multiple methods including ssGSEA, MCPcounter, and EPIC.

Conclusion: This is the first attempt to study a B cells-related prognostic signature, which is instrumental in the exploration of novel prognostic biomarkers in PAAD.

Keywords: B cells; WGCNA; pancreatic adenocarcinoma; prognostic signature; ssGSEA.

Grants and funding

This work was supported by National Natural Science Foundation of China (No. 81960439 and No. 81960119).