Presence of PD-1 similarity genes in monocytes may promote the development of type 1 diabetes mellitus and poor prognosis of pancreatic cancer.

INTRODUCTION

To identify proteins and corresponding genes that share sequential and structural similarity with programmed cell death protein-1 (PD-1) in patients with type 1 diabetes mellitus (T1DM) via bioinformatics analysis.

RESEARCH DESIGN AND METHODS

All proteins with immunoglobulin V-set domain were screened in the human protein sequence database, and the corresponding genes were obtained in the gene sequence database. GSE154609 was downloaded from the GEO database, which contained peripheral blood CD14+ monocyte samples from patients with T1DM and healthy controls. The difference result and the similar genes were intersected. Analysis of gene ontology and Kyoto encyclopedia of genes and genomes pathways was used to predict potential functions using the R package 'cluster profiler'. The expression differences of intersected genes were analyzed in The Cancer Genome Atlas pancreatic cancer dataset and GTEx database using t-test. The correlation between the overall survival and disease-free progression of patients with pancreatic cancer was analyzed using Kaplan-Meier survival analysis.

RESULTS

2068 proteins with immunoglobulin V-set domain similar to PD-1 and 307 corresponding genes were found. 1705 upregulated differentially expressed genes (DEGs) and 1335 downregulated DEGs in patients with T1DM compared with healthy controls were identified. A total of 21 genes were overlapped with the 307 PD-1 similarity genes, including 7 upregulated and 14 downregulated. Of these, mRNA levels of 13 genes were significantly increased in patients with pancreatic cancer. High expression of and was significantly correlated with shorter overall survival of patients with pancreatic cancer, while high expression of , , and was significantly correlated with shorter disease-free survival of patients with pancreatic cancer.

CONCLUSIONS

Genes encoding immunoglobulin V-set domain similar to PD-1 may contribute to the occurrence of T1DM. Of these genes, and may serve as potential biomarkers for the prognosis of pancreatic cancer.