【摘要】 目的:探讨连接蛋白43(CX43)基因表达在胶质瘤中的临床意义、预后价值及其在肿瘤免疫微环境中的作用。方法:基于癌症基因组图谱(TCGA)数据库胶质瘤病人的mRNA数据及相关临床信息,利用R语言统计分析CX43基因在592例具有不同病理特征的胶质瘤患者间的表达差异。采用Kaplan-Meier生存分析法评价其预后价值,基因集富集分析(GSEA)探究CX43在胶质瘤中的潜在作用机制,用CIBERSORTx分析CX43 mRNA与胶质瘤免疫细胞浸润的关系。最后利用34例术后石蜡标本进行免疫组化验证分析。结果:与对照组比较,CX43 mRNA在异柠檬酸脱氢酶野生型、染色体1p/19q无共缺失的样本中表达水平显著升高(P<0.01)。CX43高表达的胶质瘤患者预后较差(P<0.01)。GSEA结果提示CX43 mRNA高表达组在9个特征基因集中富集。CIBERSORTx免疫浸润分析提示CX43 mRNA高表达组中单核细胞、巨噬细胞M2表型、活化树突状细胞显著升高(P<0.05)。免疫组化结果提示CX43蛋白高表达与1p/19q无共缺失相关,并伴CD163阳性的M2样巨噬细胞增多。结论:CX43高表达与胶质瘤1p/19q无共缺失病理分型相关,为胶质瘤不良预后因子,且可能具有诱导巨噬细胞向M2表型极化的作用。更多还原

【Abstract】 OBJECTIVE: To investigate clinical significance, prognostic value and immune cell infiltration from connexin 43(CX43) gene expression in gliomas. METHODS:Based on collected mRNA data and related clinical information among glioma patients in the Cancer Genome Atlas,the R language was used to analyze differential expressions of the CX43 gene in 592 patients. The Kaplan-Meier survival analysis method was used to evaluate its prognostic value. The Gene set enrichment analysis(GSEA) was used to explore potential mechanisms of CX43 involvement in glioma. Relationships between CX43 mRNA expression and immune cells infiltration into glioma were investigated using the CIBERSORTx algorithm. Finally,34 postoperative specimens were used for immunohistochemical analyses. RESULTS: Expression levels of CX43 mRNA were significantly increased in the wild-type isocitrate dehydrogenase and the chromosome 1 p/19 q nonco-deletion groups(P<0.01). Prognosis of glioma patients with high expression of CX43 were poor(P<0.01).GSEA results indicate that the high CX43 mRNA expression group showed enrichment in a 9 hallmark gene set. CIBERSORTx immune infiltration analyses show that monocytes, macrophages, M2 phenotypes, and activated dendritic cells were significantly increased in the high CX43 mRNA expression group(P<0.05).Results from the immunohistochemistry analyses indicate that high expressions of the CX43 protein were related to the absence of 1 p/19 q co-deletion and the increased CD163-positive M2-like macrophages. CONCLUSION:Our results indicate that high expression of CX43 was related to the pathological classification of glioma 1 p/19 q without co-deletion, to poor prognostic for glioma and to inducing macrophages to polarize to the M2 phenotype.更多还原