关键词: CXCL9 M1 macrophage cervical cancer chemokine coexpression gene

Mesh : Uterine Cervical Neoplasms / genetics pathology metabolism Humans Female Chemokine CXCL9 / genetics metabolism Gene Expression Regulation, Neoplastic Macrophages / metabolism Prognosis Gene Regulatory Networks Protein Interaction Maps / genetics Computational Biology Tumor-Associated Macrophages / metabolism Gene Expression Profiling Databases, Genetic

来  源:   DOI:10.1080/01443615.2024.2373951

Abstract:
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
Cervical cancer is a common gynaecological malignancy, investigating the precise gene expression regulation of M1 macrophage is crucial for understanding the changes in the immune microenvironment of cervical cancer. In our study, a total of 82 coexpression genes with M1 macrophages were identified, and these genes were involved in the production and biological processes of chemokines and chemokine receptors. Especially, the chemokine CXCL9 was positively correlated with M1 macrophage infiltration levels in cervical cancer. CXCL9 as a protective factor, it manifestly expressed in blood immune cells, and was positively related to immune checkpoints. CXCL9 amplification was the most common type of mutation. And CXCL9 expression could have an effect on the sensitivity of some chemicals or targeted drugs against cervical cancer. These findings may provide new insight into the M1 macrophage coexpression gene network and molecular mechanisms, and shed light on the role of CXCL9 in cervical cancer.
摘要:
M1巨噬细胞共表达基因在宫颈癌中的表达和功能尚未确定。在宫颈癌中,表达CXCL9的肿瘤相关巨噬细胞的报道很少。
为阐明M1巨噬细胞在宫颈癌中的调控基因网络,我们在TCGA数据库中下载了宫颈癌患者的基因表达谱,以鉴定M1巨噬细胞共表达基因.然后通过STRING数据库构建蛋白质-蛋白质相互作用网络,并进行功能富集分析,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来全面调查共表达基因CXCL9,包括蛋白质印迹法和免疫组织化学法,遗传狂躁症,Kaplan-Meier绘图仪,Xenashiny,TISC12,ACLBI,HPA,TISIB,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趋化因子和趋化因子受体的产生和功能。尤其是,CXCL9与M1巨噬细胞浸润水平呈正相关。CXCL9的表达会显著降低,高CXCL9水平与宫颈癌肿瘤患者的良好预后有关。它在血液免疫细胞中明显表达,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的信号通路,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抵抗。
我们的发现可能为宫颈癌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巨噬细胞关联基因CXCL9可能是宫颈癌治疗的良好预后基因和潜在治疗靶点。
宫颈癌是一种常见的妇科恶性肿瘤,研究M1巨噬细胞的精确基因表达调控对于了解宫颈癌免疫微环境的变化至关重要。在我们的研究中,共鉴定出82个与M1巨噬细胞共表达的基因,这些基因参与趋化因子和趋化因子受体的产生和生物学过程。尤其是,在宫颈癌中,趋化因子CXCL9与M1巨噬细胞浸润水平呈正相关.CXCL9作为保护因子,它在血液免疫细胞中明显表达,与免疫检查点呈正相关。CXCL9扩增是最常见的突变类型。CXCL9的表达可能影响某些化学物质或靶向药物对宫颈癌的敏感性。这些发现可能为M1巨噬细胞共表达基因网络和分子机制提供新的见解。并阐明CXCL9在宫颈癌中的作用。
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