The Diagnostic and Immunotherapeutic Value of CD248 in Renal Cell Carcinoma

Abstract

Background: Renal cell carcinoma (RCC) is the most common malignancy in the urinary system. Despite substantial improvements in available treatment options, the survival outcome of advanced RCC is unsatisfactory. Identifying novel biomarkers to assist in early diagnosis and to screen patients who are sensitive to immunotherapy would be beneficial. CD248 is a promising candidate that deserves to be investigated.Methods: The Cancer Genome Atlas (TCGA) data set and clinical specimens were adopted to analyze the expression of CD248 between normal and tumor tissues. Univariate and multivariate Cox regression analyses were employed to identify independent prognostic factors and construct a CD248-based prognostic signature. The correlation among the present signature, tumor-infiltrating immune cells (TIICs), the tumor mutation burden (TMB), and immunomodulatory molecules was evaluated. The weighted gene co-expression network analysis (WGCNA), the enrichment analysis, and the miRNA correlation analysis were performed to explore the underlying mechanism of CD248 in the progression of RCC.Results: The overexpression of CD248 in RCC was related to a poor prognosis, and a CD248-based prognostic signature could precisely stratify patients with RCC with different survival outcomes regardless of the training or testing cohort. The present signature could reflect the immunosuppressive landscape of RCC (i.e., increased infiltration of regulatory T cells and upregulated immune checkpoints), accompanied by deteriorated clinicopathologic indexes. The TMB and immunostimulatory molecules expression also increased with the risk score generated from the present signature. CD248 co-expressed gene sets were identified through the WGCNA algorithm, and several immunosuppressive Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were significantly enriched. The result of CD248-correlated miRNA further emphasized the importance of CD248 in RCC.Conclusion: CD248 is a valuable biomarker to improve the diagnostic and therapeutic efficiency of RCC. The immunosuppressive effect of CD248 co-expressed genes may provide insight for the present study, and miRNA would help to reveal the mechanism of the expressive regulation of CD248.

Prognostic Value of Vascular-Expressed PSMA and CD248 in Urothelial Carcinoma of the Bladder

“…Pericytes provide structural support for endothelial cells and thus stabilize the vasculature. In our previous study, we found that CD248 was expressed specifically in HCC and RCC, and overexpression of CD248 was related to a poor prognosis ( 31 , 32 ). Davies et al.…”

“…In our previous study, we found that PSMA and CD248 were both expressed specifically in the vasculature in hepatocellular carcinoma (HCC), and vascular-expressed PSMA and CD248 might be used as prognostic markers and vascular therapeutic targets for HCC (30,31). We also found that overexpression of CD248 in renal cell carcinoma (RCC) was related to poor prognosis (32). Therefore, we wondered whether vascular-expressed PSMA and CD248 could be promising biomarkers for UCB.…”

CD248 as a bridge between angiogenesis and immunosuppression: a promising prognostic and therapeutic target for renal cell carcinoma

“…In short, a CD248-based prognostic signature has an excellent ability to predict the prognosis of patients with AUC =0.889 (16). Therefore, CD248 might bridge the gap between angiogenesis and immunosuppression, and thus be a promising prognostic and therapeutic target for RCC.…”

“…Our previous study indicated that the overexpression of CD248 could reflect an immunosuppressive TME and is inversely correlated with the prognosis of patients with RCC (16). In this paper, we further analyzed the gene expression profiles and clinical information of RCC patients both from The Cancer Genome Atlas (TCGA) and clinical records.…”

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“…Pericytes provide structural support for endothelial cells and thus stabilize the vasculature. In our previous study, we found that CD248 was expressed specifically in HCC and RCC, and overexpression of CD248 was related to a poor prognosis (31,32). Davies et al (51) reported that overexpression of CD248 correlated negatively with the clinical outcome of patients with breast cancer.…”