Immunohistological Examination of HEATR1 and SLC27A2 Expression in ccRCC Samples to Evaluate Their Potential as...

Background/Objectives: Clear cell renal cell carcinoma (ccRCC) is a common kidney cancer with limited therapeutic options. This study investigated the expression of HEAT repeat-containing protein 1 (HEATR1) and solute carrier family 27 member 2 (SLC27A2) in ccRCC and their potential as prognostic markers and therapeutic targets. Methods: Analysis of a public proteomic dataset (CPTAC) and immunohistochemistry (IHC) validation in an independent cohort of 52 ccRCC patients was performed. HEATR1 and SLC27A2 expression were correlated with survival outcomes. Reactome pathway analysis was conducted to explore the functional roles of HEATR1 and SLC27A2. Results: The analysis showed that HEATR1 is upregulated and associated with poor prognosis, while SLC27A2 is downregulated and similarly linked to shorter progression-free survival. High HEATR1 expression and low SLC27A2 expression correlated with shorter progression-free survival (PFS) and overall survival (OS) in patients with high-grade ccRCC. Reactome analysis indicated HEATR1's involvement in RNA metabolism and SLC27A2's role in lipid metabolism, particularly peroxisomal lipid metabolism and fatty acyl-CoA biosynthesis. HEATR1 exhibited a dual localization in both the cytoplasm and nucleus, while SLC27A2 was primarily observed at the cell membrane and the nucleus. This different subcellular distribution suggests multifaceted roles for both proteins in ccRCC pathogenesis. Conclusions: HEATR1 and SLC27A2 are potential prognostic markers in ccRCC. Further research is needed to validate these findings in larger, more diverse cohorts and elucidate their roles in ccRCC progression.