Association of HLA-DRA expression with prognosis and tumor microenvironment in clear cell renal cell carcinoma

Recombinant human leukocyte antigen class II histocompatibility antigen (HLA-DRA) has been implicated in the development of various cancers, but its specific role in clear cell renal cell carcinoma (ccRCC) remains unclear.Tissue samples and clinicopathological data from 78 ccRCC patients were collected. Immunohistochemical staining and H-Score analysis were performed to evaluate HLA-DRA expression and its association with clinicopathological features and prognosis. A survival prediction model incorporating multiple clinical and pathological variables was developed. Immune infiltration analysis explored HLA-DRA's role in the tumor microenvironment at the single-cell level, while pathway enrichment analyses identified chemicals, genes, and co-expressed genes associated with HLA-DRA. HLA-DRA expression was significantly higher in ccRCC tissues compared to adjacent normal tissues. Elevated HLA-DRA expression correlated with the Fuhrman nuclear grade and was associated with poor prognosis, as demonstrated by Kaplan-Meier and Cox regression analyses. Diagnostic and prognostic models, including ROC curve and nomogram analyses, highlighted HLA-DRA's predictive value. Immune infiltration analysis revealed strong associations between HLA-DRA expression and the infiltration of lymphocytes, chemokines, and chemokine receptors, with single-cell studies pinpointing monocyte macrophages as the primary source of HLA-DRA expression. Co-expression and pathway enrichment analyses suggested that HLA-DRA contributes to ccRCC pathogenesis and progression through diverse pathways. Additionally, several chemicals were identified as modulators of HLA-DRA expression.HLA-DRA plays a pivotal role in ccRCC diagnosis, prognosis, and immune regulation, highlighting its potential as a biomarker and therapeutic target.