Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
J Obstet Gynaecol. 2024 Dec;44(1):2373951. doi: 10.1080/01443615.2024.2373951. Epub 2024 Jul 4.
The expression and function of coexpression genes of M1 macrophage in cervical cancer have not been identified. And the CXCL9-expressing tumour-associated macrophage has been poorly reported in cervical cancer.
To clarify the regulatory gene network of M1 macrophage in cervical cancer, we downloaded gene expression profiles of cervical cancer patients in TCGA database to identify M1 macrophage coexpression genes. Then we constructed the protein-protein interaction networks by STRING database and performed functional enrichment analysis to investigate the biological effects of the coexpression genes. Next, we used multiple bioinformatics databases and experiments to overall investigate coexpression gene CXCL9, including western blot assay and immunohistochemistry assay, GeneMANIA, Kaplan-Meier Plotter, Xenashiny, TISCH2, ACLBI, HPA, TISIDB, GSCA and cBioPortal databases.
There were 77 positive coexpression genes and 5 negative coexpression genes in M1 macrophage. The coexpression genes in M1 macrophage participated in the production and function of chemokines and chemokine receptors. Especially, CXCL9 was positively correlated with M1 macrophage infiltration levels in cervical cancer. CXCL9 expression would significantly decrease and high CXCL9 levels were linked to good prognosis in the cervical cancer tumour patients, it manifestly expressed in blood immune cells, and was positively related to immune checkpoints. CXCL9 amplification was the most common type of mutation. The CXCL9 gene interaction network could regulate immune-related signalling pathways, and CXCL9 amplification was the most common mutation type in cervical cancer. Meanwhile, CXCL9 may had clinical significance for the drug response in cervical cancer, possibly mediating resistance to chemotherapy and targeted drug therapy.
Our findings may provide new insight into the M1 macrophage coexpression gene network and molecular mechanisms in cervical cancer, and indicated that M1 macrophage association gene CXCL9 may serve as a good prognostic gene and a potential therapeutic target for cervical cancer therapies.
宫颈癌中 M1 巨噬细胞的共表达基因的表达和功能尚未确定。而且，在宫颈癌中，表达 CXCL9 的肿瘤相关巨噬细胞报道较少。
为了阐明宫颈癌中 M1 巨噬细胞的调控基因网络，我们从 TCGA 数据库中下载了宫颈癌患者的基因表达谱，以鉴定 M1 巨噬细胞的共表达基因。然后，我们通过 STRING 数据库构建了蛋白质-蛋白质相互作用网络，并进行了功能富集分析，以研究共表达基因的生物学效应。接下来，我们使用多个生物信息学数据库和实验对共表达基因 CXCL9 进行了全面研究，包括 Western blot 检测和免疫组织化学检测、GeneMANIA、Kaplan-Meier Plotter、Xenashiny、TISCH2、ACLBI、HPA、TISIDB、GSCA 和 cBioPortal 数据库。
M1 巨噬细胞中有 77 个阳性共表达基因和 5 个阴性共表达基因。M1 巨噬细胞中的共表达基因参与了趋化因子和趋化因子受体的产生和功能。特别是，CXCL9 与宫颈癌中 M1 巨噬细胞浸润水平呈正相关。在宫颈癌患者中，CXCL9 的表达会显著降低，高 CXCL9 水平与较好的预后相关，它在血液免疫细胞中明显表达，并与免疫检查点呈正相关。CXCL9 扩增是最常见的突变类型。CXCL9 基因相互作用网络可以调节免疫相关信号通路，CXCL9 扩增是宫颈癌中最常见的突变类型。同时，CXCL9 可能对宫颈癌的药物反应具有临床意义，可能介导对化疗和靶向药物治疗的耐药性。
我们的研究结果可能为宫颈癌中 M1 巨噬细胞共表达基因网络和分子机制提供新的见解，并表明 M1 巨噬细胞相关基因 CXCL9 可能作为宫颈癌的一个良好预后基因和潜在治疗靶点。
