GJA1 Expression and Its Prognostic Value in Cervical Cancer.

GJA1 Expression and Its Prognostic Value in Cervical Cancer.
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GJA1表达及其在宫颈癌中的预后价值。

DOI:
10.1155/2020/8827920
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发表时间:
2020
影响因子:
--
通讯作者:
Li S
Li S
中科院分区:
生物学3区
文献类型:
--
作者:
Meng S;Fan X;Zhang J;An R;Li S

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间隙连接蛋白α 1(GJA 1)属于差距连接家族,在肿瘤中已被广泛研究。我们使用来自癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)的公开数据评估了GJA 1在宫颈癌(CC)中的作用。采用基因表达谱交互分析(Gene Expression Profiling Interactive Analysis,GEPIA)、6个GEO数据集和人类蛋白质图谱(Human Protein Atlas,HPA)分析GJA 1在CC和正常组织中的表达差异。采用卡方检验和Logistic回归分析GJA 1表达与临床病理特征的关系。Kaplan-Meier生存分析和考克斯比例风险回归分析用于评估GJA 1表达对生存的影响。采用基因集富集分析(GSEA)筛选GJA 1调控的信号通路。选择免疫细胞特异性识别器(ImmuCellAI)来分析受GJA 1影响的免疫细胞。基于GEPIA、GEO数据集和HPA,GJA 1在CC中的表达显著低于正常组织。卡方检验和logistic回归分析均显示GJA 1高表达与角化、激素使用、肿瘤大小和FIGO分期显著相关。Kaplan-Meier曲线提示GJA 1高表达提示预后不良(p = 0.0058)。多变量分析显示,GJA 1高表达是总生存率差的独立预测因子(HR,4.084; 95%CI,1.354-12.320; p = 0.013)。GSEA显示许多与癌症相关的通路,如p53信号通路和Wnt信号通路,在GJA 1高表达组中富集。免疫细胞丰度分析显示,在高GJA 1表达组中,CD 8幼稚、DC和中性粒细胞的丰度显著增加。结论:GJA 1可作为CC患者预后不良的标志物和治疗靶点。此外,许多与癌症相关的通路可能是GJA 1调控的关键通路。此外,GJA 1可以影响免疫细胞的丰度。
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 (p = 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; p = 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.
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