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CAPG 过表达与卵巢癌不良预后和免疫抑制细胞浸润相关

英文原题:Overexpression of CAPG Is Associated with Poor Prognosis and Immunosuppressive Cell Infiltration in Ovarian Cancer.

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Overexpression of CAPG Is Associated with Poor Prognosis and Immunosuppressive Cell Infiltration in Ovarian Cancer.

PubMed 2022/02/09(内容时间) Dis Markers

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中文摘要

历史上,免疫疗法对晚期卵巢癌患者仅能产生部分缓解,导致临床疗效不佳。全面了解卵巢癌中免疫相关基因表达和免疫细胞浸润,将有助于改进免疫疗法的实施。Capping Actin Protein, Gelsolin-Like (CAPG) 基因编码一种肌动蛋白调节蛋白,在肿瘤进展和免疫调节中发挥重要作用。

本研究旨在确定 CAPG 在卵巢癌中的潜在治疗和预后作用。从 TCGA、Oncomine、GEPIA、UALCAN 和 Kaplan-Meier plotter 收集的数据中研究了 CAPG 表达和临床信息。通过 LinkedOmics、GeneMANIA 和 NetworkAnalyst 评估了 CAPG 共表达网络。通过 TIMER、ImmuCellAI 和 GEPIA 分析了 CAPG 与免疫浸润的相关性。

我们的结果显示,肿瘤 CAPG 高表达的患者 5 年总生存期显著缩短。功能富集分析表明,CAPG 相关表型主要涉及炎症反应、趋化因子和细胞因子信号传导、细胞黏附以及 Toll 样受体信号通路。在卵巢癌中,CAPG 表达与调节性 T 细胞 (Tregs)、肿瘤相关巨噬细胞 (TAMs) 和耗竭 T 细胞 (Texs) 的浸润水平呈正相关,而与自然杀伤 T 细胞 (NKTs) 和中性粒细胞的浸润水平呈负相关。

此外,FOXP3、CD25、CD127、CCR8和TGFβ在Tregs中的表达;CCL2和CD68在TAM中的表达;CD163、VSIG4和MS4A4A在M2巨噬细胞中的表达;CD33和CD11b在髓源性抑制细胞(MDSCs)中的表达;以及PD1、CTLA4、LAG3、TIM3、GZMB、2B4和TIGIT在Texs中的表达,均与卵巢癌中CAPG的表达显著相关。这些发现表明,CAPG可能促进卵巢癌的免疫抑制性肿瘤微环境,导致T细胞耗竭表型和肿瘤进展。

因此,CAPG可作为判断卵巢癌预后和免疫治疗效果的潜在生物标志物。

展开英文摘要原文

Historically, immunotherapies have only resulted in a partial response from patients with advanced ovarian cancer, resulting in poor clinical efficacy. A full understanding of immune-related gene expression and immunocyte infiltration in ovarian cancer would be instrumental for the improved implementation of immunotherapy. The Capping Actin Protein, Gelsolin-Like ( CAPG ) gene encodes an actin-regulatory protein, which plays important roles in tumor progression and immune regulation.

This study is aimed at identifying the potential therapeutic and prognostic roles of CAPG in ovarian cancer. CAPG expression and clinical information were investigated in the data collected from TCGA, Oncomine, GEPIA, UALCAN, and Kaplan-Meier plotter. CAPG coexpression networks were evaluated by LinkedOmics, GeneMANIA, and NetworkAnalyst. The correlation of CAPG with immune infiltrates was analyzed via TIMER, ImmuCellAI, and GEPIA.

Our result showed that patients with high tumoral CAPG expression had significantly shorter 5-year overall survival. Functional enrichment analysis indicated that CAPG -related phenotypes were largely involved in inflammatory response, chemokine and cytokine signaling, cell adhesion, and Toll-like receptor signaling pathways.

CAPG expression was positively correlated with infiltrating levels of regulatory T cells (Tregs), tumor-associated macrophages (TAMs), and exhausted T cells (Texs) while being negatively correlated with infiltrating levels of natural killer T cells (NKTs) and neutrophils in ovarian cancer.

Moreover, the expression of FOXP3 , CD25 , CD127 , CCR8 , and TGFβ in respect to Tregs; CCL2 and CD68 in respect to TAM; CD163 , VSIG4 , and MS4A4A in respect to M2 macrophages; CD33 and CD11b in respect to myeloid-derived suppressor cells (MDSCs); and PD1 , CTLA4 , LAG3 , TIM3 , GZMB , 2B4 , and TIGIT in respect to Texs was significantly correlated with CAPG expression in ovarian cancer.

These findings suggest that CAPG may contribute to the immunosuppressive tumor microenvironment in ovarian cancer, leading to an exhausted T cell phenotype and tumor progression.

Therefore, CAPG can be used as a potential biomarker for determining prognosis and immunotherapy effectiveness in ovarian cancer.

论文信息

作者
Jiang S、Yang Y、Zhang Y、Ye Q、Song J、Zheng M、Li X
单位
Department of Gynecology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, China.China
文献类型
已撤稿
期刊
Disease markers2022
原文标识
PubMed 35186171 · DOI 10.1155/2022/9719671