Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Department of Dermatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Biomed Res Int. 2020 Nov 24;2020:8827920. doi: 10.1155/2020/8827920. eCollection 2020.
Gap Junction Protein Alpha 1 (GJA1) belongs to the gap junction family and has been widely studied in cancers. We evaluated the role of GJA1 in cervical cancer (CC) using public data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. The difference of GJA1 expression level between CC and normal tissues was analyzed by the Gene Expression Profiling Interactive Analysis (GEPIA), six GEO datasets, and the Human Protein Atlas (HPA). The relationship between clinicopathological features and GJA1 expression was analyzed by the chi-squared test and the logistic regression. Kaplan-Meier survival analysis and Cox proportional hazard regression analysis were used to assessing the effect of GJA1 expression on survival. Gene set enrichment analysis (GSEA) was used to screen the signaling pathways regulated by GJA1. Immune Cell Abundance Identifier (ImmuCellAI) was chosen to analyze the immune cells affected by GJA1. The expression of GJA1 in CC was significantly lower than that in normal tissues based on the GEPIA, GEO datasets, and HPA. Both the chi-squared test and the logistic regression showed that high-GJA1 expression was significantly correlated with keratinization, hormone use, tumor size, and FIGO stage. The Kaplan-Meier curves suggested that high-GJA1 expression could indicate poor prognosis ( = 0.0058). Multivariate analysis showed that high-GJA1 expression was an independent predictor of poor overall survival (HR, 4.084; 95% CI, 1.354-12.320; = 0.013). GSEA showed many cancer-related pathways, such as the p53 signaling pathway and the Wnt signaling pathway, were enriched in the high-GJA1-expression group. Immune cell abundance analysis revealed that the abundance of CD8 naive, DC, and neutrophil was significantly increased in the high-GJA1-expression group. In conclusion, GJA1 can be regarded as a potential prognostic marker of poor survival and therapeutic target in CC. Moreover, many cancer-related pathways may be the critical pathways regulated by GJA1. Furthermore, GJA1 can affect the abundance of immune cells.
间隙连接蛋白α 1（GJA1）属于间隙连接家族，在癌症中研究广泛。我们使用癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）中的公共数据评估 GJA1 在宫颈癌（CC）中的作用。通过基因表达谱交互式分析（GEPIA）、六个 GEO 数据集和人类蛋白质图谱（HPA）分析 CC 和正常组织之间 GJA1 表达水平的差异。卡方检验和逻辑回归分析分析了 GJA1 表达与临床病理特征的关系。Kaplan-Meier 生存分析和 Cox 比例风险回归分析用于评估 GJA1 表达对生存的影响。基因集富集分析（GSEA）用于筛选 GJA1 调节的信号通路。选择免疫细胞丰度鉴定器（ImmuCellAI）分析受 GJA1 影响的免疫细胞。基于 GEPIA、GEO 数据集和 HPA，CC 中 GJA1 的表达明显低于正常组织。卡方检验和逻辑回归均显示，高 GJA1 表达与角化、激素使用、肿瘤大小和 FIGO 分期显著相关。Kaplan-Meier 曲线表明，高 GJA1 表达可预示不良预后（=0.0058）。多因素分析显示，高 GJA1 表达是总生存期不良的独立预测因子（HR，4.084；95%CI，1.354-12.320；=0.013）。GSEA 显示，高 GJA1 表达组中富集了许多癌症相关通路，如 p53 信号通路和 Wnt 信号通路。免疫细胞丰度分析显示，高 GJA1 表达组中 CD8 幼稚细胞、DC 和中性粒细胞的丰度显著增加。总之，GJA1 可作为 CC 中预后不良的潜在预后标志物和治疗靶点。此外，许多癌症相关通路可能是 GJA1 调节的关键通路。此外，GJA1 可以影响免疫细胞的丰度。
