GNG4, as a potential predictor of prognosis, is correlated with immune infiltrates in colon adenocarcinoma

IF 5.3 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Journal of Cellular and Molecular Medicine Pub Date : 2023-07-13 DOI:10.1111/jcmm.17847
Juan Wang, Yanshuang Wang, Jiaming Zhou, Mengmeng Cai, Peng Guo, Tongde Du, Hui Zhang
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Abstract

The tumour microenvironment (TME) and immunosuppression play an important role in colon cancer (CC) metastasis, which seriously affects the prognosis of CC. G protein subunit gamma 4 (GNG4) has been shown to participate in tumour progression and the tumour mutation burden (TMB) in colorectal cancer. However, the effect of GNG4 on the CC TME and immunology remains elusive. Weighted gene coexpression network analysis (WGCNA) was employed for screening aberrantly expressed genes associated with the immune score, and GNG4 was then selected through prognostic and immune correlation analysis. Based on RNA sequencing data obtained from the TCGA and GEO databases, the expression pattern and immune characteristics of GNG4 were comprehensively examined using a pan-cancer analysis. Upregulation of GNG4 was linked to an adverse prognosis and immune inhibitory phenotype in CC. Pan-cancer analysis demonstrated higher GNG4 expression in tumours than in paired normal tissue in human cancers. GNG4 expression was closely related to prognosis, TMB, immune checkpoints (ICPs), microsatellite instability (MSI) and neoantigens. GNG4 promoted CC cell proliferation, migration and invasion and participated in immune regulation in the TME. Significantly, GNG4 expression was found to negatively correlate with tumour-infiltrating immune cells, ICP, TMB and MSI in CC. GNG4 expression predicted the immunotherapy response in the IMvigor210 cohort, suggesting that GNG4 could be used as a potential biomarker in CC for prognostication and immunology. Moreover, the expression of GNG4 predicted the immunotherapy response of ICB in CC.

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GNG4作为一种潜在的预后预测因子,与结肠腺癌的免疫浸润相关
肿瘤微环境(tumor microenvironment, TME)和免疫抑制在结肠癌(colorectal cancer, CC)转移中起重要作用,严重影响CC的预后,G蛋白亚单位γ - 4 (GNG4)参与结直肠癌的肿瘤进展和肿瘤突变负荷(tumor mutation burden, TMB)。然而,GNG4对CC TME和免疫学的影响尚不清楚。采用加权基因共表达网络分析(Weighted gene co - expression network analysis, WGCNA)筛选与免疫评分相关的异常表达基因,通过预后和免疫相关性分析选择GNG4。基于TCGA和GEO数据库中获得的RNA测序数据,采用泛癌分析方法全面检查GNG4的表达模式和免疫特性。GNG4的上调与CC的不良预后和免疫抑制表型有关。泛癌症分析表明,人类癌症肿瘤中GNG4的表达高于配对正常组织。GNG4的表达与预后、TMB、免疫检查点(ICPs)、微卫星不稳定性(MSI)和新抗原密切相关。GNG4在TME中促进CC细胞增殖、迁移和侵袭,参与免疫调节。值得注意的是,GNG4的表达与CC的肿瘤浸润免疫细胞、ICP、TMB和MSI呈负相关,在IMvigor210队列中,GNG4的表达预测了免疫治疗的反应,这表明GNG4可以作为CC预后和免疫学的潜在生物标志物。此外,GNG4的表达预测了CC中ICB的免疫治疗反应。
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来源期刊
CiteScore
10.00
自引率
1.90%
发文量
496
审稿时长
28 weeks
期刊介绍: Bridging physiology and cellular medicine, and molecular biology and molecular therapeutics, Journal of Cellular and Molecular Medicine publishes basic research that furthers our understanding of the cellular and molecular mechanisms of disease and translational studies that convert this knowledge into therapeutic approaches.
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