Overexpression of CAPG Is Associated with Poor Prognosis and Immunosuppressive Cell Infiltration in Ovarian Cancer.
Overexpression of CAPG Is Associated with Poor Prognosis and Immunosuppressive Cell Infiltration in Ovarian Cancer.
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CAPG 的过度表达与卵巢癌的不良预后和免疫抑制细胞浸润相关
DOI：
10.1155/2022/9719671
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Jiang S;Yang Y;Zhang Y;Ye Q;Song J;Zheng M;Li X
从历史上看，免疫疗法只能在晚期卵巢癌患者中产生部分反应，导致临床疗效不佳。充分了解免疫相关基因表达和免疫细胞浸润在卵巢癌中的作用，将有助于改善免疫治疗的实施。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起重要作用。本研究旨在确定CAPG在卵巢癌中的潜在治疗和预后作用。通过TCGA、Oncomine、GEPIA、UALCAN和Kaplan-Meier绘图仪收集数据，研究CAPG的表达和临床信息。使用LinkedOmics、GeneMANIA和NetworkAnalyst对CAPG共表达网络进行评估。通过TIMER、ImmuCellAI和GEPIA分析CAPG与免疫浸润的相关性。我们的研究结果显示，肿瘤CAPG高表达的患者的5年总生存期明显缩短。功能富集分析表明，capg相关表型主要参与炎症反应、趋化因子和细胞因子信号通路、细胞粘附和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（tam）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；有关TAM的CCL2及CD68；CD163、VSIG4和MS4A4A对M2巨噬细胞的影响；CD33和CD11b对髓源性抑制细胞（MDSCs）的影响；卵巢癌中与Texs相关的PD1、CTLA4、LAG3、TIM3、GZMB、2B4、TIGIT与CAPG表达显著相关。这些发现表明，CAPG可能有助于卵巢癌的免疫抑制肿瘤微环境，导致T细胞表型耗竭和肿瘤进展。因此，CAPG可作为卵巢癌预后和免疫治疗效果的潜在生物标志物。
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.
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影响因子：
254.7
作者：
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通讯作者：
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