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FAM46C作为泛癌预后和预测免疫治疗疗效的潜在标志物。

FAM46C as a Potential Marker for Pan-Cancer Prognosis and Predicting Immunotherapeutic Efficacy.

作者信息

Deng Jiehua, Xiao Wei, Wang Zheng

机构信息

Centre of Imaging Diagnosis, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China.

Department of Clinical Medicine, Medical College of Shihezi University, Shihezi, China.

出版信息

Front Genet. 2022 Feb 9;13:810252. doi: 10.3389/fgene.2022.810252. eCollection 2022.

Abstract

is a common mutated gene in tumours. A comprehensive understanding of the relationship between expression and pan-cancer can guide clinical prognosis and broaden the immunotherapeutic targets. Data from The Cancer Genome Atlas and Genotype-Tissue Expression (GTEx) databases were obtained, and gene expression of different tumour types and stages was analysed. Immunohistochemical analysis was performed to detect differences in the protein levels in normal and cancerous tissues. The genetic variation of was characterised using cBioPortal. The clinical prognostic value of and the impact of expression levels on the prognosis of patients with different types of cancer were assessed based on Kaplan-Meier and Cox regression analyses. Gene set enrichment analysis (GSEA) was used to analyse the pathways associated with . Correlations between expression levels and immune infiltration were assessed using the TIMER2 database and CIBERSORT algorithm, and correlations between expression and the ESTIMATE, immune and stromal scores were analysed using the ESTIMATE algorithm. In addition, we also analysed the correlation between expression and immune activation, suppression genes and immune chemokines. The expression level of was correlated with the prognosis of most tumours, and low expression levels often suggested a poor prognosis. was positively correlated with the abundance of CD4 T cells, CD8 T cells and plasma B lymphocytes in the tumour microenvironment. exhibited a strong correlation with immunomodulatory pathways, immunomodulatory factors and immune markers. In addition, high expression correlated with tumour mutational burden in acute myeloid leukaemia and microsatellite instability in endometrial cancer. Our study suggests that can be a potential prognostic marker for pan-cancer, is closely associated with immune regulation and may be an immune checkpoint to guide future clinical immunotherapy.

摘要

是肿瘤中一种常见的突变基因。全面了解其表达与泛癌之间的关系可指导临床预后并拓宽免疫治疗靶点。获取了来自癌症基因组图谱(The Cancer Genome Atlas)和基因型-组织表达(Genotype-Tissue Expression,GTEx)数据库的数据,并分析了不同肿瘤类型和阶段的基因表达。进行免疫组织化学分析以检测正常组织和癌组织中该蛋白水平的差异。使用cBioPortal对其基因变异进行了表征。基于Kaplan-Meier和Cox回归分析评估了其临床预后价值以及其表达水平对不同类型癌症患者预后的影响。基因集富集分析(Gene set enrichment analysis,GSEA)用于分析与该基因相关的通路。使用TIMER2数据库和CIBERSORT算法评估其表达水平与免疫浸润之间的相关性,并使用ESTIMATE算法分析其表达与ESTIMATE、免疫和基质评分之间的相关性。此外,我们还分析了其表达与免疫激活、抑制基因和免疫趋化因子之间的相关性。该基因的表达水平与大多数肿瘤的预后相关,低表达水平通常提示预后不良。它与肿瘤微环境中CD4 T细胞、CD8 T细胞和浆B淋巴细胞的丰度呈正相关。它与免疫调节通路、免疫调节因子和免疫标志物表现出强烈的相关性。此外,在急性髓系白血病中其高表达与肿瘤突变负担相关,在子宫内膜癌中与微卫星不稳定性相关。我们的研究表明,该基因可以作为泛癌的潜在预后标志物,与免疫调节密切相关,可能是一个免疫检查点,以指导未来的临床免疫治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0198/8864238/8bc692b9463c/fgene-13-810252-g001.jpg

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