Comprehensive analysis of fatty acid desaturase 3 in clear cell renal cell carcinoma: insights into tumor progression, immune microenvironment, and clinical outcomes

BackgroundClear cell renal cell carcinoma (ccRCC or KIRC) is a malignant neoplasm characterized by reprogrammed lipid metabolism. Fatty acid desaturase 3 (FADS3), a sphingoid Δ14Z desaturase, is required for the synthesis of unsaturated fatty acids in tumor biology.

However, the role of FADS3 in ccRCC progression and prognosis and in modulating the tumor immune microenvironment (TIME) remains to be elucidated.MethodsThe ccRCC transcriptomic datasets were obtained from the TCGA, GEO, and GTEx databases. Mendelian randomization (MR) and single-cell RNA sequencing analyses were used to investigate the associations of FADS3 with lipid metabolism, and differential expression genes in ccRCC.

Bioinformatics analysis was also used to investigate the association of FADS3 expression with tumor progression, prognosis, TIME, and potential pathogenic mechanism in ccRCC. FADS3 expression in ccRCC cell lines was confirmed by qRT-PCR, western blotting, RNA-Seq.

FADS3 roles in ccRCC were assessed by functional assays including cell proliferation, migration, invasion, and colony formation using wild-type and FADS3-knockdown cell lines.ResultsLipid metabolism was found to be upregulated in ccRCC tumor tissues based on comprehensive bioinformatic analysis.