Bioinformatics analysis of the clinical significance of HLA class II in breast cancer

Abstract

Human leukocyte antigen (HLA) class II plays critical roles in antigen presentation and the initiation of immune responses. However, the correlation between the HLA class II gene expression level and the survival of patients with breast cancer is still under investigation. We analyzed microarray and RNA-Seq data of breast cancer from the cancer genome atlas (TCGA), genotype-tissue expression (GTEx) and Oncomine databases by using bioinformatics tools. The expression of the HLA-DQA1, HLA-DQA2, and HLA-DQB2 genes was significantly upregulated in breast cancer. Higher expression levels of HLA class II genes in breast cancer, especially HLA-DOB and HLA-DQB2, were significantly associated with better overall survival. Furthermore, the expression of HLA class II genes was more closely associated with survival in breast cancer than in other cancer types. CD48 coexpressed with both HLA-DOB and HLA-DQB2 was also positively associated with the overall survival of breast cancer patients. The results indicated that HLA class II and CD48 may enhance antitumor immunity, and their expression patterns may serve as potential prognostic biomarkers and therapeutic targets in breast cancer.Abbreviations: CRC = colorectal cancer, DAVID = database for annotation, visualization and integrated discovery, GEPIA2 = gene expression profiling interactive analysis 2, GO = gene ontology, GTEx = genotype-tissue expression, HLA = human leukocyte antigen, HR = hazard ratio, OS = overall survival, STRING = search tool for the retrieval of interacting genes, TCGA = the cancer genome atlas.

PanCanSurvPlot: A Large-scale Pan-cancer Survival Analysis Web Application

“…Taking the survival analysis of CD48 in the TCGA-BRCA dataset in the TCGA database and the GSE26304 breast cancer dataset in the GEO database as examples, the user obtains the results shown in Figures 3A and B. The CD48 high expression group in both datasets had a longer overall survival (OS), which validated the previous findings[28].…”

Molecular subtype identification and prognosis stratification based on lysosome-related genes in breast cancer

“…Additionally, GDI2 is a target of paclitaxel through the p75NTR signaling pathway in prostate cancer tumorigenesis [ 23 ]. HLA-DQB2 has been shown to be highly expressed in breast cancer and predicts better overall survival [ 24 ]. Plasma HSP90AA1 has been found to predict the risk of breast cancer incidence and distant metastasis [ 25 ].…”

Human Leukocyte Antigen-Allelic Variations May Influence the Age at Cancer Diagnosis in Lynch Syndrome

“…Although we found a statistically significant association between rare binned HLA-DPB1 alleles (HLA-DPB1*09:01, HLA-DPB1*10:01, HLA-DPB1*106:01, HLA-DPB1*18:01, HLA-DPB1*20:01, HLA-DPB1*26:01, HLA-DPB1*28:01, HLA-DPB1*296:01, and HLA-DPB1*55:01) and young age at cancer diagnosis, additional investigation for these HLA alleles in a large cohort of LSVH is required to further complement and validate our findings. While HLA class II is traditionally associated with presenting antigens from extracellular pathogens, it also plays a role in presenting tumor antigens [ 56 , 57 ]. It has been reported that HLA class II antigen expression by tumor cells can influence the tumor antigen (TA)-specific immune responses [ 56 ].…”