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泛癌分析揭示SGO1作为一种潜在的癌症预后和免疫生物标志物。

Pan-cancer analysis reveals SGO1 as a potential cancer prognostic and immunological biomarker.

作者信息

Wang Yongqiang, Long Xianming, Zhang Long, Zhou Fangfang, Zhong Miaochun

机构信息

Institutes of Biology and Medical Science, Soochow University, Suzhou, China.

Department of Rheumatology and Immunology, The First Affiliated Hospital of Soochow University, Suzhou, China.

出版信息

J Cancer. 2025 Jul 24;16(11):3372-3388. doi: 10.7150/jca.115334. eCollection 2025.

Abstract

Shugoshin 1 (SGO1) is primarily known for its critical functions in chromosome segregation during cell division, protecting cohesin complexes and ensuring accurate mitotic processes. Previous studies have reported SGO1's regulatory roles in isolated cancer types, but its pan-cancer significance and underlying mechanisms remain undefined. This study systematically investigates SGO1 in 33 cancer types, integrating multi-omics analyses and functional validation to reveal its role as a pan-cancer biomarker and therapeutic target. Using TCGA, GEPIA2, and HPA databases, we found SGO1 was significantly overexpressed in 19 cancer types compared to normal tissues. High SGO1 expression correlated with poorer overall survival (OS) and disease-free survival (DFS) in more than 10 cancers, validated by Kaplan-Meier analysis. Genomic analysis revealed frequent SGO1 mutations and DNA methylation dysregulation, while immune profiling showed associations with immune cell infiltration (B cells, CD8+ T cells) and PD-1/PD-L1 checkpoint genes. Protein-protein interaction and enrichment analyses uncovered BUB1 as a key co-expressed gene, suggesting a role in spindle checkpoint regulation. Functional assays in breast cancer cell line MDA-MB-231 and lung cancer cell line A549 showed SGO1 knockdown inhibited proliferation, migration, and invasion, with xenograft models confirming reduced tumor growth. Our findings establish SGO1 as a novel pan-cancer biomarker, linking its expression to tumor progression, immune evasion, and genomic instability. This study bridges bioinformatics with functional validation, offering new mechanistic insights and therapeutic avenues for SGO1-driven cancers.

摘要

守护蛋白1(SGO1)主要因其在细胞分裂过程中染色体分离的关键功能而闻名,它保护黏连蛋白复合体并确保有丝分裂过程准确无误。以往研究报道了SGO1在个别癌症类型中的调控作用,但其泛癌意义及潜在机制仍不明确。本研究对33种癌症类型中的SGO1进行了系统研究,整合多组学分析和功能验证,以揭示其作为泛癌生物标志物和治疗靶点的作用。利用TCGA、GEPIA2和HPA数据库,我们发现与正常组织相比,SGO1在19种癌症类型中显著过表达。超过10种癌症中,SGO1高表达与较差的总生存期(OS)和无病生存期(DFS)相关,Kaplan-Meier分析验证了这一点。基因组分析揭示了SGO1频繁发生突变以及DNA甲基化失调,而免疫图谱分析显示其与免疫细胞浸润(B细胞、CD8 + T细胞)以及PD-1/PD-L1检查点基因有关。蛋白质-蛋白质相互作用和富集分析发现BUB1是关键的共表达基因,提示其在纺锤体检查点调控中发挥作用。在乳腺癌细胞系MDA-MB-231和肺癌细胞系A549中的功能试验表明,敲低SGO1可抑制细胞增殖、迁移和侵袭,异种移植模型证实肿瘤生长减缓。我们的研究结果确立了SGO1作为一种新型泛癌生物标志物的地位,将其表达与肿瘤进展、免疫逃逸和基因组不稳定联系起来。本研究将生物信息学与功能验证相结合,为SGO1驱动的癌症提供了新的机制见解和治疗途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2f3/12374945/3304721ab81f/jcav16p3372g001.jpg

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