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凝溶胶蛋白超家族基因在子宫内膜癌诊断、预后及免疫微环境调节中的意义

Significance of Gelsolin Superfamily Genes in Diagnosis, Prognosis and Immune Microenvironment Regulation for Endometrial Cancer.

作者信息

Jiang Senwei, Ye Minjuan, Wan Jing, Ye Qingjian, Qiu Suli, Yang Yuebo, Li Xiaomao

机构信息

Department of Gynecology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

出版信息

Cancer Med. 2025 Feb;14(4):e70584. doi: 10.1002/cam4.70584.

DOI:10.1002/cam4.70584
PMID:39964147
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11834165/
Abstract

BACKGROUND

Previously, anti-CTLA4 and anti-PD-1/PD-L1 immunotherapies have shown limited efficacy in MSI-H/MMR-D endometrial cancer, leading to poor clinical outcomes. The gelsolin superfamily, which includes GSN, SCIN, VILL, VIL1, CAPG, AVIL, SVIL, and FLII, plays crucial roles in cell motility and gene regulation.

AIMS

The objective of this study is to explore the potential therapeutic and prognostic implications of the gelsolin superfamily in EC.

MATERIALS & METHODS: Data from TCGA, GEPIA, THPA, UALCAN, and Kaplan-Meier plotter databases were analyzed to investigate the expression and clinical relevance of gelsolin superfamily members. Co-expression networks of the gelsolin superfamily were assessed using LinkedOmics, GeneMANIA, and NetworkAnalyst. The relationship between gelsolin superfamily and immune cell infiltration was investigated using TIMER, ImmuCellAI, and GEPIA.

RESULTS

We found that high expressions of CAPG, AVIL, and SVIL were associated with poor prognosis, while high expressions of GSN and FLII were linked to better outcomes in EC. Functional enrichment analysis indicated the involvement of gelsolin superfamily members in pathways related to estrogen response, MYC targets, epithelial-mesenchymal transition, TGF beta signaling, MTORC1 signaling, oxidative phosphorylation, inflammatory response, and IL6-JAK-STAT3 signaling. Furthermore, gelsolin superfamily members demonstrated strong correlations with the levels of monocytes, natural killer T, naive CD4+ T, follicular helper T, and central memory T in EC. In vitro studies showed that silencing CAPG and FLII could inhibit proliferation and metastasis in endometrial cancer cell lines.

CONCLUSION

These findings indicate the significant association of gelsolin superfamily members with prognosis and immunological status in endometrial cancer.

摘要

背景

此前，抗CTLA4和抗PD-1/PD-L1免疫疗法在微卫星高度不稳定/错配修复缺陷（MSI-H/MMR-D）子宫内膜癌中显示出有限的疗效，导致临床预后不佳。凝溶胶蛋白超家族包括凝溶胶蛋白（GSN）、肌动蛋白切割蛋白（SCIN）、绒毛蛋白（VILL）、绒毛蛋白1（VIL1）、帽蛋白（CAPG）、丝状肌动蛋白结合蛋白（AVIL）、 supervillin（SVIL）和Flightless-1（FLII），在细胞运动和基因调控中起关键作用。

目的

本研究的目的是探讨凝溶胶蛋白超家族在子宫内膜癌（EC）中的潜在治疗和预后意义。

材料与方法

分析来自癌症基因组图谱（TCGA）、基因表达谱交互分析（GEPIA）、人类蛋白质图谱（THPA）、UALCAN和Kaplan-Meier Plotter数据库的数据，以研究凝溶胶蛋白超家族成员的表达及其与临床的相关性。使用LinkedOmics、GeneMANIA和NetworkAnalyst评估凝溶胶蛋白超家族的共表达网络。使用肿瘤免疫估计资源（TIMER）、免疫细胞人工智能（ImmuCellAI）和GEPIA研究凝溶胶蛋白超家族与免疫细胞浸润之间的关系。

结果

我们发现，CAPG、AVIL和SVIL的高表达与预后不良相关，而GSN和FLII的高表达与EC的较好预后相关。功能富集分析表明，凝溶胶蛋白超家族成员参与了与雌激素反应、MYC靶点、上皮-间质转化、转化生长因子β信号传导、哺乳动物雷帕霉素靶蛋白复合物1（MTORC1）信号传导、氧化磷酸化、炎症反应和白细胞介素6-信号转导及转录激活因子3（IL6-JAK-STAT3）信号传导相关的通路。此外，凝溶胶蛋白超家族成员与EC中单核细胞、自然杀伤T细胞、初始CD4+T细胞、滤泡辅助性T细胞和中央记忆T细胞的水平密切相关。体外研究表明，沉默CAPG和FLII可抑制子宫内膜癌细胞系的增殖和转移。

结论

这些发现表明凝溶胶蛋白超家族成员与子宫内膜癌的预后和免疫状态密切相关。

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