Department of Oncology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, China.
State Key Laboratory of Proteomics, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China.
J Cell Mol Med. 2023 Sep;27(17):2517-2532. doi: 10.1111/jcmm.17847. Epub 2023 Jul 13.
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.
肿瘤微环境（TME）和免疫抑制在结肠癌（CC）转移中起着重要作用，严重影响 CC 的预后。G 蛋白亚基γ4（GNG4）已被证明参与肿瘤进展和结直肠癌的肿瘤突变负担（TMB）。然而，GNG4 对 CC 的 TME 和免疫学的影响仍不清楚。采用加权基因共表达网络分析（WGCNA）筛选与免疫评分相关的异常表达基因，然后通过预后和免疫相关性分析选择 GNG4。基于 TCGA 和 GEO 数据库获得的 RNA 测序数据，通过泛癌分析综合检查 GNG4 的表达模式和免疫特征。GNG4 的上调与 CC 预后不良和免疫抑制表型有关。泛癌分析表明，GNG4 在人类癌症中的肿瘤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 促进 CC 细胞增殖、迁移和侵袭，并参与 TME 中的免疫调节。值得注意的是，在 CC 中，GNG4 的表达与肿瘤浸润免疫细胞、ICP、TMB 和 MSI 呈负相关。GNG4 的表达预测了 IMvigor210 队列中的免疫治疗反应，表明 GNG4 可作为 CC 中用于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。
