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.
背景/目的：透明细胞肾细胞癌（ccRCC）是一种常见的肾癌，治疗选择有限。本研究探讨了含HEAT重复序列蛋白1（HEATR1）和溶质载体家族27成员2（SLC27A2）在ccRCC中的表达情况，及其作为预后标志物和治疗靶点的潜力。 方法：分析公共蛋白质组学数据集（CPTAC），并在一个包含52例ccRCC患者的独立队列中进行免疫组织化学（IHC）验证。将HEATR1和SLC27A2的表达与生存结局进行相关性分析，并通过Reactome通路分析探讨HEATR1和SLC27A2的功能作用。 结果：分析显示，HEATR1表达上调且与不良预后相关，而SLC27A2表达下调，同样与较短的无进展生存期相关。在高分级ccRCC患者中，HEATR1高表达和SLC27A2低表达与较短的无进展生存期（PFS）和总生存期（OS）相关。Reactome分析表明，HEATR1参与RNA代谢，而SLC27A2在脂质代谢中发挥作用，尤其是过氧化物酶体脂质代谢和脂肪酰辅酶A生物合成。HEATR1在细胞质和细胞核中均有分布，而SLC27A2主要定位于细胞膜和细胞核。这种不同的亚细胞分布提示这两种蛋白在ccRCC发病机制中具有多方面的作用。 结论：HEATR1和SLC27A2是ccRCC的潜在预后标志物。未来需要在更大、更多样化的队列中验证这些发现，并阐明它们在ccRCC进展中的作用。
肿瘤(癌症)患者之家