目的 应用生物信息学方法对CHAC1与泛癌临床预后及免疫相关性进行预测分析,探讨CHAC1对泛癌生物学特性的影响。方法 利用多种数据库分析CHAC1在泛癌中的表达差异、生存分析和免疫细胞浸润、肿瘤干性评分（tumor stemness score,DNAss）、肿瘤突变负荷（tumor mutational burden,TMB）及微卫星不稳定性（microsatellite instability,MSI）,通过Western blot验证CHAC1在胃癌、肺癌以及结肠癌细胞系中的表达,通过IHC验证CHAC1在胃癌及癌旁组织中的表达。结果 CHAC1在多种肿瘤中高表达,且CHAC1高表达的患者预后更差,Western blot及IHC结果显示,CHAC1在肿瘤中呈高表达（P<0.05）。浸润分化簇的CD8+细胞、CD4+细胞、中性粒细胞、树突状细胞和巨噬细胞聚集显示与CHAC1表达相关,DNA甲基化、DNAss 、TMB、MSI亦与CHAC1的高表达有关。结论 CHAC1可作为多种肿瘤有价值的预后生物标志物和治疗的新靶标。CHAC1可能在免疫逃逸和免疫检查点抑制剂治疗中具有重要意义,然而,还需要进一步的研究来证实。
Abstract
Objective To explore the potential role of CHAC1 in pan-cancer biology by analyzing its correlation with clinical prognosis and immune characteristics using bioinformatics methods. Methods Data from multiple databases were used to investigate the differential expression of CHAC1 across various cancers, survival analysis, immune cell infiltration, tumor stemness score (DNAss), tumor mutational burden (TMB), and microsatellite instability (MSI) were also evaluated in relation to CHAC1 expression. Western blot analysis was employed to determine CHAC1 expression levels in gastric, lung, and colon cancer cell lines, while immunohistochemistry (IHC) was utilized to evaluate CHAC1 expression in human gastric carcinoma tissues and corresponding adjacent non-tumor tissues. Results CHAC1 was found to be highly expressed in multiple tumor types, with patients exhibiting poorer prognosis. The results of Western blot and IHC demonstrated that CHAC1 is highly expressed in gastric cancer. Immune cell infiltration, including CD8+ cells, CD4+ cells, neutrophils, dendritic cells, and macrophages, was significantly correlated with CHAC1 expression. Additionally, DNA methylation, DNAss, TMB, and MSI were found to be associated with CHAC1 expression levels. Conclusion CHAC1 may serve as a valuable prognostic biomarker and a potential therapeutic target for multiple cancers. Its role in immune filtration and immune checkpoint inhibitor therapy warrants further investigation.
关键词
CHAC1 /
泛癌 /
生物信息学 /
免疫细胞浸润
Key words
CHAC1 /
pan-cancer /
bioinformatics /
immune cell infiltration
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基金
张家界市科技发展专项项目“MIA3编码TANGO1蛋白与胃癌的关系”[2022（09）]
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