SGOL1 在肾透明细胞癌中的预后和生物学功能：多组学分析。

BACKGROUND: Shugoshin-1 (SGOL1) is a mammalian ortholog of Shugoshin in yeast and is essential for precise chromosome segregation during mitosis and meiosis. Aberrant SGOL1 expression was reported to be closely correlated with the malignant progression of various tumors. However, the expression pattern and biological function of SGOL1 in clear cell renal cell carcinoma (ccRCC) are unclear. METHODS: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases provide mRNA expression data and outcome information for ccRCC patients. Immunohistochemistry (IHC) of ccRCC tissue chips verified SGOL1 protein expression in ccRCC patients. Data processing and visualization were performed with the UALCAN, TISIDB, TIMER, GSCA, LinkedOmics, and starBase databases. Gene Ontology (GO) annotation and gene set enrichment analysis (GSEA) were used to identify SGOL1-related biological functions and signaling pathways. Immune infiltration analysis was performed using the TISIDB database, ssGSEA algorithm, and TCGA-KIRC cohort. The biological role of SGOL1 in ccRCC was investigated using a series of in vitro cytological assays, including the MTT assay, EdU staining assay, flow cytometry analysis, Transwell assay, and wound healing assay. RESULTS: SGOL1 was highly expressed in ccRCC and linked to adverse clinicopathological parameters and unfavorable prognosis. Multivariate logistic regression and nomogram calibration suggested that SGOL1 might serve as an independent and reliable prognostic predictor of ccRCC. Functional enrichment analysis indicated that SGOL1 may be involved in the cell cycle, the p53 pathway, DNA replication, and T-cell activation. Furthermore, tumor microenvironment (TME) analysis suggested that SGOL1 was positively associated with Treg infiltration and immune checkpoint upregulation. In addition, we identified a potential SNHG17/PVT1/ZMIZ1-AS1-miR-23b-3p-SGOL1 axis correlated with ccRCC carcinogenesis and progression. Finally, we demonstrated that SGOL1 promoted ccRCC cell proliferation, migratory capacity, and invasion in vitro. CONCLUSIONS: SGOL1 potentially functions as an oncogene in ccRCC progression and might contribute to the immunosuppressive TME by increasing Treg infiltration and checkpoint expression, suggesting that targeting SGOL1 could be a novel therapeutic strategy for the treatment of ccRCC patients.

背景：Shugoshin-1（SGOL1）是酵母中 Shugoshin 的哺乳动物同源物，对于有丝分裂和减数分裂期间的精确染色体分离至关重要。据报道，异常的 SGOL1 表达与各种肿瘤的恶性进展密切相关。然而，SGOL1 在透明细胞肾细胞癌（ccRCC）中的表达模式和生物学功能尚不清楚。

方法：癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）提供了 ccRCC 患者的 mRNA 表达数据和结局信息。免疫组织化学（IHC）检测 ccRCC 组织芯片验证了 SGOL1 蛋白在 ccRCC 患者中的表达。使用 UALCAN、TISIDB、TIMER、GSCA、LinkedOmics 和 starBase 数据库进行数据处理和可视化。基因本体（GO）注释和基因集富集分析（GSEA）用于鉴定与 SGOL1 相关的生物学功能和信号通路。使用 TISIDB 数据库、ssGSEA 算法和 TCGA-KIRC 队列进行免疫浸润分析。使用一系列体外细胞学测定，包括 MTT 测定、EdU 染色测定、流式细胞术分析、Transwell 测定和划痕愈合测定，研究了 SGOL1 在 ccRCC 中的生物学作用。

结果：SGOL1 在 ccRCC 中高表达，并与不良临床病理参数和不良预后相关。多变量逻辑回归和列线图校准表明，SGOL1 可能是 ccRCC 的独立可靠预后预测因子。功能富集分析表明，SGOL1 可能参与细胞周期、p53 通路、DNA 复制和 T 细胞激活。此外，肿瘤微环境（TME）分析表明，SGOL1 与 Treg 浸润和免疫检查点上调呈正相关。此外，我们鉴定了一个潜在的 SNHG17/PVT1/ZMIZ1-AS1-miR-23b-3p-SGOL1 轴与 ccRCC 发生和进展相关。最后，我们证明 SGOL1 促进了 ccRCC 细胞在体外的增殖、迁移和侵袭。

结论：SGOL1 可能在 ccRCC 进展中发挥癌基因作用，并通过增加 Treg 浸润和检查点表达促进免疫抑制性 TME，提示靶向 SGOL1 可能成为治疗 ccRCC 患者的新治疗策略。