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胶质瘤中免疫浸润相关 RBMS1 的表达谱及预后相关性:一项多维整合分析

英文原题:Expression profile and prognostic relevance of immune infiltration-related RBMS1 in gliomas: a multidimensional integrative analysis.

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Expression profile and prognostic relevance of immune infiltration-related RBMS1 in gliomas: a multidimensional integrative analysis.

PubMed 2025/07/08(内容时间) J Cancer Res Clin Oncol Q2 · IF 3.3(JCR 2025)

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研究概要

RBMS1 在胶质瘤中异常过表达,与肿瘤侵袭性、免疫抑制微环境重塑及不良预后相关,使其成为有前景的预后生物标志物和治疗靶点。

研究思路结论见上方概要

本研究探讨RNA结合基序单链相互作用蛋白1(RBMS1)在胶质瘤中的表达特征及其与临床病理特征、免疫浸润和预后的关联,旨在评估其作为预后生物标志物的潜力。

从GEO数据集GSE43378和GSE178621中筛选差异表达基因(DEGs)(阈值:P < 0.05,|logFC|> 1),并通过TCGA和GEPIA数据库验证RBMS1。使用TISIDB评估RBMS1与免疫浸润之间的相关性。还使用GEPIA探讨了RBMS1与免疫检查点分子、共刺激基因和趋化因子之间的相关性。对165例胶质瘤和62例正常脑组织进行免疫组织化学(IHC)染色,以分析RBMS1表达及其临床病理相关性(WHO分级、远处转移)。使用Kaplan-Meier(K-M)曲线和log-rank检验评估三年生存结局,包括总生存期(OS)和无复发生存期(RFS)。此外,进行单因素和多因素Cox回归分析以评估独立预后因素。

综合生物信息学分析确定RBMS1是一个关键DEG,在胶质瘤中显著上调(TCGA和GEPIA:P < 0.05),并与免疫细胞浸润呈中度正相关(Tregs:r = 0.461;NKTs:r = 0.505;Th1:r = 0.451;均P < 0.001)。RBMS1还与关键免疫检查点分子(PDCD1、CD274、CTLA4等)、共刺激基因(CD28、TNFRSF9)和趋化因子(CXCL9、CXCL10、CCL5)呈显著正相关,提示其可能在调节免疫微环境中发挥作用。临床上,RBMS1阳性在胶质瘤中明显高于对照组(59.39% vs. 16.13%,χ 2 = 33.822,P < 0.001),与晚期WHO分级(P < 0.001)和远处转移(30.62% vs. 14.93%,P = 0.021)相关。单因素分析显示,RBMS1表达、WHO分级、肿瘤位置、切除范围和转移与预后相关。生存分析显示,RBMS1阳性患者的3年OS(34.69% vs. 70.15%)和RFS显著更差(均P < 0.001)。Cox回归分析证实,RBMS1是OS的独立预后因素(P = 0.028,HR = 1.845,95% CI:1.068-3.188),WHO分级和转移也是独立预后因素。

展开英文摘要原文

This study investigates the expression characteristics of RNA binding motif single stranded interacting protein 1 (RBMS1) in gliomas and its associations with clinicopathological features, immune infiltration, and prognosis, aiming to evaluate its potential as a prognostic biomarker.

Differentially expressed genes (DEGs) were screened from the GEO datasets GSE43378 and GSE178621 (thresholds: P < 0.05,|logFC|> 1), with RBMS1 validated via the TCGA and GEPIA databases. Correlations between RBMS1 and immune infiltration were assessed using the TISIDB. Correlations between RBMS1 and immune checkpoint molecules, costimulatory genes, and chemokines were also explored using GEPIA. Immunohistochemistry (IHC) was performed on 165 glioma and 62 normal brain tissues to analyze RBMS1 expression and its clinicopathological relevance (WHO grade, distant metastasis). Three-year survival outcomes were evaluated using Kaplan-Meier (K-M) curves and log-rank tests for overall survival (OS) and relapse-free survival (RFS). Additionally, univariate and multivariate Cox regression analyses were conducted to assess independent prognostic factors.

Integrated bioinformatic analysis identified RBMS1 as a key DEG, showing significant upregulation in gliomas (TCGA and GEPIA: P < 0.05) and moderate positive correlations with immune cell infiltration (Tregs: r = 0.461; NKTs: r = 0.505; Th1: r = 0.451; all P < 0.001). RBMS1 also showed significant positive correlations with key immune checkpoint molecules (PDCD1, CD274, CTLA4, etc.), costimulatory genes (CD28, TNFRSF9), and chemokines (CXCL9, CXCL10, CCL5), suggesting its potential role in modulating the immune microenvironment. Clinically, RBMS1 positivity was markedly higher in gliomas than controls (59.39% vs. 16.13%, χ 2 = 33.822, P < 0.001), correlating with advanced WHO grades (P < 0.001) and distant metastasis (30.62% vs. 14.93%, P = 0.021). Univariate analysis revealed that RBMS1 expression, WHO grade, tumor location, extent of resection, and metastasis were associated with prognosis. Survival analysis revealed significantly worse 3-year OS (34.69% vs. 70.15%) and RFS in RBMS1-positive patients (both P < 0.001). Cox regression analysis confirmed that RBMS1 was an independent prognostic factor for OS (P = 0.028, HR = 1.845, 95% CI: 1.068-3.188), along with WHO grade and metastasis.

RBMS1 is aberrantly overexpressed in gliomas, associated with tumor aggressiveness, immunosuppressive microenvironment remodeling, and poor prognosis, positioning it as a promising prognostic biomarker and therapeutic target.

论文信息

作者
Zhang Y、Zhou Y、Zhang S、Zhou L
第一作者单位
Department of Pediatric Neurosurgery, West China Second University Hospital, Sichuan University, Chengdu, 610041, China.China
通讯作者单位
Department of Neurosurgery, West China Hospital, Sichuan University, No. 37, Guoxue Lane, Wuhou District, Chengdu, 610044, Sichuan, China. zhlxlll@163.com.China
期刊
Journal of cancer research and clinical oncology2025 Jul 8
原文标识
PubMed 40629190 · DOI 10.1007/s00432-025-06254-2