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肾透明细胞癌样本中HEATR1和SLC27A2表达的免疫组织学检查以评估其作为预后标志物的潜力——一项初步研究

Immunohistological Examination of HEATR1 and SLC27A2 Expression in ccRCC Samples to Evaluate Their Potential as Prognostic Markers-A Preliminary Study.

作者信息

Kasperczak Michał, Kołodziejczak-Guglas Iga, Pawłowska-Kasperczak Karolina, Wiznerowicz Maciej, Antczak Andrzej

机构信息

Department of Urology, J. Struś Hospital in Poznań, Szwajcarska 3, 61285 Poznań, Poland.

International Institute for Molecular Oncology, 60203 Poznań, Poland.

出版信息

Cancers (Basel). 2025 Jul 3;17(13):2234. doi: 10.3390/cancers17132234.

Abstract

: 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. : 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. : 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. : 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.

摘要

透明细胞肾细胞癌(ccRCC)是一种常见的肾癌,治疗选择有限。本研究调查了含HEAT重复序列蛋白1(HEATR1)和溶质载体家族27成员2(SLC27A2)在ccRCC中的表达及其作为预后标志物和治疗靶点的潜力。:对一个公共蛋白质组数据集(CPTAC)进行了分析,并在一个由52例ccRCC患者组成的独立队列中进行了免疫组织化学(IHC)验证。HEATR1和SLC27A2的表达与生存结果相关。进行了Reactome通路分析以探索HEATR1和SLC27A2的功能作用。:分析表明,HEATR1上调且与预后不良相关,而SLC27A2下调且同样与无进展生存期缩短有关。在高级别ccRCC患者中,高HEATR1表达和低SLC27A2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,SLC27A2在脂质代谢中起作用,特别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表现出双重定位,而SLC27A2主要在细胞膜和细胞核中观察到。这种不同的亚细胞分布表明这两种蛋白质在ccRCC发病机制中具有多方面的作用。:HEATR1和SLC27A2是ccRCC潜在的预后标志物。需要进一步的研究在更大、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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d5/12249168/64235230a7b3/cancers-17-02234-g001.jpg

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