Meng Silu, Liu Yuhuan, Wang Xiaoyan, Wu Xue, Xie Wan, Kang Xiaoyan, Liu Xiaoyu, Guo Lili, Wang Changyu
Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Oncol. 2022 Jul 21;12:907960. doi: 10.3389/fonc.2022.907960. eCollection 2022.
To evaluate the prognostic value and explore the biological significance of gap junction protein beta 2 (GJB2 or Cx26) in cervical cancer (CC).
We first compared GJB2 expression between CC and normal tissues using public databases and immunohistochemistry (IHC). Based on The Cancer Genome Atlas data (TCGA cohort, n = 304) and tissue microarray samples (OBC cohort, n = 111), we explored the prognostic value of GJB2 for CC patients using bioinformatics analysis and IHC scoring. To explore the biological significance of GJB2, Gene set enrichment analysis (GSEA) and Gene Ontology (GO) were performed. The impact of GJB2 on the immune microenvironment was analyzed by CIBERSORTx and ESTIMATE algorithms. We finally investigated the relationship between GJB2 and drug sensitivity based on the Genomics of Drug Sensitivity in Cancer (GDSC).
The expression of GJB2 was significantly increased in CC over normal tissues. Both the TCGA and OBC cohort found that patients with high GJB2 expression had shorter overall survival (OS) time, and high GJB2 expression was the independent risk factor for prognosis (TCGA: HR, 2.566; 95% CI, 1.066-6.180; p = 0.036; OBC: HR, 2.198; 95% CI, 1.019-4.741; p = 0.045). GJB2 was correlated with patient clinical factors such as tumor size and differentiation grade. The p53 signaling pathway and toll-like receptor pathway may be regulated by GJB2. The abundance of various immune cells was significantly different between the low and high GJB2 expression groups. The ImmuneScore was significantly increased in the high GJB2 expression group. In addition, the expression level of GJB2 was positively correlated with the natural log of the half-maximal inhibitory concentration (LN_IC50) value of cisplatin/paclitaxel (Spearman r = 0.238/0.153, p < 0.001).
GJB2 can serve as a potential prognostic marker of poor survival and a therapeutic target in CC. Moreover, GJB2 may affect the immune microenvironment and is correlated with chemoresistance.
评估间隙连接蛋白β2（GJB2或Cx26）在宫颈癌（CC）中的预后价值并探索其生物学意义。
我们首先使用公共数据库和免疫组织化学（IHC）比较CC组织和正常组织中GJB2的表达。基于癌症基因组图谱数据（TCGA队列，n = 304）和组织微阵列样本（OBC队列，n = 111），我们使用生物信息学分析和IHC评分探索GJB2对CC患者的预后价值。为了探索GJB2的生物学意义，进行了基因集富集分析（GSEA）和基因本体论（GO）分析。通过CIBERSORTx和ESTIMATE算法分析GJB2对免疫微环境的影响。我们最终基于癌症药物敏感性基因组学（GDSC）研究了GJB2与药物敏感性之间的关系。
与正常组织相比，CC组织中GJB2的表达显著增加。TCGA和OBC队列均发现，GJB2高表达的患者总生存期（OS）较短，且GJB2高表达是预后的独立危险因素（TCGA：HR，2.566；95%CI，1.066 - 6.180；p = 0.036；OBC：HR，2.198；95%CI，1.019 - 4.741；p = 0.045）。GJB2与肿瘤大小和分化程度等患者临床因素相关。p53信号通路和Toll样受体通路可能受GJB2调控。GJB2低表达组和高表达组之间各种免疫细胞的丰度存在显著差异。高GJB2表达组的免疫评分显著升高。此外，GJB2的表达水平与顺铂/紫杉醇的半数最大抑制浓度自然对数（LN_IC50）值呈正相关（Spearman r = 0.238/0.153，p < 0.001）。
GJB2可作为CC患者生存不良的潜在预后标志物和治疗靶点。此外，GJB2可能影响免疫微环境并与化疗耐药相关。
