背景：清除型肾癌是肾癌中最常见、最致命的一种形式，占新病例的80%。虽然报道称GTSE1在多种肿瘤中高表达，并与恶性进展和不良临床预后有关，但其在ccRCC中的临床意义、与免疫细胞浸润的相关性以及生物学功能仍不清楚。方法：使用多个数据库，包括TCGA、GEO、TIMER和UALCAN Kaplan-Meier生存分析，基因集富集分析、基因本体富集Gene Ontology和京都基因与基因组百科全书（KEGG）进行GTSE1的基因表达、临床病理特征和临床意义的分析。使用TCGA-KIRC剖面提取和分析肿瘤浸润免疫细胞和免疫调节因子。使用STRING网站构建蛋白质-蛋白质相互作用。采用ccRCC组织芯片进行免疫组化检测ccRCC患者的GTSE1蛋白水平。最后进行MTT测定、集落形成实验、细胞流式细胞术分析、EdU染色实验、创伤愈合实验以及Transwell迁移和侵袭实验，评估GTSE1在体外的生物学功能。结果：GTSE1在ccRCC组织和细胞中高表达，GTSE1过表达与不良临床病理因素和不良临床预后相关。同时，功能富集分析表明，GTSE1及其共表达的基因主要与细胞周期、DNA复制和免疫反应相关，如T细胞激活和先天性免疫应答，通过多种信号通路，包括P53信号通路和T细胞受体信号通路。此外，我们观察到GTSE1表达与ccRCC浸润免疫细胞水平之间存在显著关系。生物学功能研究表明，GTSE1可以通过促进细胞增殖、细胞周期转变、迁移和侵袭能力，以及降低ccRCC细胞对顺铂的敏感性，促进ccRCC的恶性进展。结论：我们的结果表明，GTSE1作为一个潜在的癌基因，可以促进ccRCC的恶性进展和顺铂耐药性。此外，高GTSE1表达有助于增加免疫细胞浸润水平，并与更差的预后有关，提供了ccRCC肿瘤治疗的潜在靶点。Copyright © 2023 Lei、Zhang、Li和Wang。

Background: Clear cell renal cell carcinoma is the most common and fatal form of kidney cancer, accounting for 80% of new cases. Although it has been reported that GTSE1 is highly expressed in a variety of tumors and associated with malignant progression and poor clinical prognosis, its clinical significance, correlations with immune cell infiltration and biological function in ccRCC are still poorly understood. Methods: The gene expression, clinicopathological features, and clinical significance of GTSE1 were analyzed using multiple databases, including TCGA, GEO, TIMER, and UALCAN Kaplan-Meier survival analysis, gene set enrichment analysis gene ontology enrichment Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed. Tumor-infiltrating immune cells and immunomodulators were extracted and analyzed using TCGA-KIRC profiles. Protein‒protein interactions were built using the STRING website. The protein level of GTSE1 in ccRCC patients was detected by immunohistochemistry using a ccRCC tissue chip. Finally, MTT assays, colony-formation assays, cell flow cytometry analyses, EdU-staining assays, wound-healing assays, and transwell migration and invasion assays were conducted to assess the biological function of GTSE1 in vitro. Results: GTSE1 was overexpressed in ccRCC tissues and cells, and GTSE1 overexpression was associated with adverse clinical-pathological factors and poor clinical prognosis. Meanwhile, the functional enrichment analysis indicated that GTSE1 and its coexpressed genes were mainly related to the cell cycle, DNA replication, and immunoreaction, such as T-cell activation and innate immune response, through multiple signaling pathways, including the P53 signaling pathway and T-cell receptor signaling pathway. Furthermore, we observed a significant relationship between GTSE1 expression and the levels of infiltrating immune cells in ccRCC. Biological functional studies demonstrated that GTSE1 could promote the malignant progression of ccRCC by promoting cell proliferation, cell cycle transition, migration, and invasion capacity and decreasing the sensitivity of ccRCC cells to cisplatin. Conclusion: Our results indicate that GTSE1, serving as a potential oncogene, can promote malignant progression and cisplatin resistance in ccRCC. Additionally, high GTSE1 expression contributes to an increased level of immune cell infiltration and is associated with a worse prognosis, providing a potential target for tumor therapy in ccRCC.Copyright © 2023 Lei, Zhang, Li and Wang.