Analysis of Peroxisomal ABCD3 Transporter as a Prognostic Factor in Clear Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma (ccRCC) is among the 10 most common cancers diagnosed in the United States. Despite its severity and aggressive nature, biomarkers that can serve as prognostic and predictive factors for ccRCC are lacking. ABCD3, a peroxisomal long-chain fatty acid transporter, has been shown to serve as a prognostic factor in both prostate and colon cancers. Thus, this study aimed to ascertain if ABCD3, which is highly expressed in kidney tissues, may also serve as a biomarker for renal cancer.

Bioinformatics and immunohistochemical staining were employed to systematically investigate the relationship between the ABCD3 gene and protein expression, the immune microenvironment, and survival outcomes in ccRCC. We extensively harnessed data from publicly available databases, including The Cancer Genome Atlas (TGCA), UALCAN, Gene Set Cancer Analysis, UCSC Xena, and various other databases.

In silico analyses of the TCGA database revealed that ABCD3 transcripts and protein levels were significantly reduced (p<0.001) across all tumors and stages. Moreover, decreased ABCD3 expression was associated with poorer patient survival [hazard ratio=0.45 (0.33-0.61), p<0.001]. Immunohistochemical and CPTAC database analyses revealed that ABCD3 was significantly downregulated in ccRCC patients (p<0.05). Multivariate Cox regression analysis revealed that ABCD3 expression is an independent factor for overall survival [HR=0.4534 (0.2859-0.7189), p<0.001].

Our findings suggest that ABCD3 is a novel biomarker for ccRCC and that the downregulation of ABCD3 expression, and other members of the peroxisomal VLCFA oxidation pathway may represent a unique molecular feature of ccRCC.