凝溶胶蛋白（GSN）作为雌激素受体阳性乳腺癌的关键调节因子：对预后、化疗敏感性和免疫浸润的影响

Gelsolin (GSN) as a key regulator in estrogen receptor-positive breast cancer: implications for prognosis, chemotherapy sensitivity, and immune infiltration.

作者信息

Lv Mian, Wang Huiling, Feng Guanqing, Nong Qingxiao, Tao Shouwen, Ma Yanfei, Fang Dalang

机构信息

Department of Breast and Thyroid Surgery, The Second People's Hospital of Nanning City, The Third Affiliated Hospital of Guangxi Medical University, Guangxi, Nanning, 530021, China.

Department of Breast Surgery, Guangxi Medical University Cancer Hospital, Nanning, 530021, Guangxi, China.

出版信息

Discov Oncol. 2025 Jul 9;16(1):1294. doi: 10.1007/s12672-025-03128-4.

DOI:10.1007/s12672-025-03128-4

PMID:40634593

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12240912/

Abstract

BACKGROUND

Gelsolin (GSN), a cytoskeletal regulatory protein implicated in cancer progression, remains understudied in estrogen receptor-positive breast cancer (ER + BC), particularly regarding its links to immune infiltration and drug resistance.

METHODS

Transcriptomic data from TCGA (616 ER + tumors, 113 normal) and Metabric (1,497 ER + cases) were analyzed. Immunohistochemistry images were sourced from the Human Protein Atlas database (HPA). Differential expression analysis (limma package), Mendelian randomization (MR) for causal inference, and colocalization (Coloc package) were employed. Drug sensitivity and immune infiltration correlations were assessed using multiple bioinformatics tools.

RESULTS

Differential expression revealed 303 upregulated and 715 downregulated genes. MR identified 276 eQTLs and 106 pQTLs, with GSN as a central key gene. Elevated GSN expression correlated with reduced ER + breast cancer risk (colocalization analysis: shared variant probability PP.H4.abf = 1.01%). Immunohistochemistry analysis demonstrated significantly lower GSN expression in ER + BC cases compared to normal samples, consistent with finding from TCGA cohorts. Higher GSN expression was linked to improved RFS in the Metabric (p = 0.023) and Kaplan-Meier datasets (p = 0.001). GSN expression was also associated with tumor size, age, and chemotherapy sensitivity for Cisplatin, Docetaxel, Doxorubicin, Etoposide, Gemcitabine, and Vinorelbine. Immune infiltration analysis showed a positive correlation between high GSN expression and the infiltration of naive B cells, but a reverse result was observed with M2 macrophage infiltration. GSN has potential as both a prognostic and therapeutic marker in ER + breast cancer, influencing immune response and drug sensitivity. Its low expression in tumors and survival benefits suggest it can help with risk assessment and treatment decisions.

摘要

背景

凝溶胶蛋白（GSN）是一种参与癌症进展的细胞骨架调节蛋白，在雌激素受体阳性乳腺癌（ER+BC）中的研究仍较少，尤其是其与免疫浸润和耐药性的联系。

方法

分析了来自TCGA（616例ER+肿瘤，113例正常样本）和Metabric（1497例ER+病例）的转录组数据。免疫组织化学图像来自人类蛋白质图谱数据库（HPA）。采用差异表达分析（limma软件包）、用于因果推断的孟德尔随机化（MR）和共定位分析（Coloc软件包）。使用多种生物信息学工具评估药物敏感性与免疫浸润的相关性。

结果

差异表达分析显示303个基因上调，715个基因下调。MR鉴定出276个表达数量性状基因座（eQTL）和106个蛋白数量性状基因座（pQTL），GSN是核心关键基因。GSN表达升高与ER+乳腺癌风险降低相关（共定位分析：共享变异概率PP.H4.abf = 1.01%）。免疫组织化学分析表明，与正常样本相比，ER+BC病例中GSN表达显著降低，这与TCGA队列的研究结果一致。在Metabric数据集（p = 0.023）和Kaplan-Meier数据集中（p = 0.001），较高的GSN表达与更好的无复发生存期相关。GSN表达还与肿瘤大小、年龄以及对顺铂、多西他赛、阿霉素、依托泊苷、吉西他滨和长春瑞滨的化疗敏感性相关。免疫浸润分析显示，高GSN表达与幼稚B细胞浸润呈正相关，但与M2巨噬细胞浸润呈相反结果。GSN在ER+乳腺癌中具有作为预后和治疗标志物的潜力，可影响免疫反应和药物敏感性。其在肿瘤中的低表达和生存获益表明它有助于风险评估和治疗决策。