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

Abstract

IntroductionTo 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 methodsAll 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.Results2068 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 ofMYOM3andHHLA2was significantly correlated with shorter overall survival of patients with pancreatic cancer, while high expression ofFGFRL1,CD274, andSPEGwas significantly correlated with shorter disease-free survival of patients with pancreatic cancer.ConclusionsGenes encoding immunoglobulin V-set domain similar to PD-1 may contribute to the occurrence of T1DM. Of these genes,MYOM3andSPEGmay serve as potential biomarkers for the prognosis of pancreatic cancer.

The Importance of HHLA2 in Solid Tumors—A Review of the Literature

“…In colorectal cancer, HHLA2 is expressed more prominently in the tumor than in healthy tissues, and similar tendencies can be observed in clear cell renal cell carcinoma, hepatic malignancies, gallbladder cancer, oral squamous cell carcinoma, lung cancer, bladder urothelial carcinoma, and thyroid cancer [13,23,25,28,36,46,48,49,66,67,72,84]. The issue is more complicated in the cases of gastric, pancreatic, and ovarian cancer, where studies present contradictory results regarding HHLA2 expression [26,42,43,81]. The associations with clinicopathological factors are also not clear and differ between tumor types.…”

“…Understanding this mechanism requires more data, and future studies should focus on the differentiation between how HHLA2 expression in tumor cells and HHLA2 expression in other cells of the tumor microenvironment can influence the course of the disease. It is worth mentioning that high HHLA2 expression in PC corresponded to shorter OS (p = 0.007), according to the TCGA database, which highlights the fact that the significance of HHLA2 expression in PC remains to be clarified [81].…”

“…Healthy cells of peritumoral tissues (duct cells, islets, and acinar cells) did not exhibit HHLA2 expression, but in pancreatic intraepithelial neoplasia (PanIN) lesions of the peritumoral area (detected in 20 out of 91 cases), HHLA2 immunohistochemical staining was mostly positive. Moreover, some inflamed ductal cells showed HHLA2 expression [39,81]. In the independent intraductal papillary mucinous neoplasm (IPMN) cohort, 70.73% of cases expressed HHLA2, but this expression was not markedly related to IPMN grade.…”