Yang Xiaojuan, Cao Xunjie, Zhu Qing, Wu Hong
Liver Digital Transformation Research Laboratory, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, 610041, Sichuan, People's Republic of China.
Abdominal Oncology Ward, Cancer Center, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
Sci Rep. 2025 Apr 28;15(1):14879. doi: 10.1038/s41598-025-96389-6.
Gap junction protein B5 (GJB5, also known as Connexin 31.1) has recently been reported to be downregulated in several cancer types, where it functions primarily as a tumor suppressor in cancers such as melanoma and non-small cell lung cancer (NSCLC). However, there no reports describing its prognostic and immunological roles in pan-cancer. This study evaluated the association of GJB5 in various cancer types by a comprehensive pan-cancer analysis. The differential GJB5 expression in tumor and adjacent tissues acquired from The Cancer Genome Atlas (TCGA) databases was compared. Furthermore, univariate Cox regression and Kaplan-Meier survival analyses were performed to assess the influence of GJB5 on the disease-specific survival (DSS), disease-free interval (DFI), clinical stage, progression-free interval (PFI), and overall survival (OS) in various cancers. Moreover, the levels of GJB5 and its activity in the tumor microenvironment were assessed via the Tumor Immune Single-cell Hub (TISCH). In addition, the biological importance of GJB5 levels in various cancers was further assessed via Gene Set Enrichment Analysis. Tumor-Immune System Interactions Database (TISIDB) and Tumor Immune Estimation Resource Database 2.0 (TIMER2.0) tools indicated that GJB5 affected the tumor's immune infiltration potential. This research also evaluated the association of GJB5 with immune features: immune modulatory genes, tumor mutational burden (TMB), and microsatellite instability (MSI). The data indicated that enhanced GJB5 level was linked to worse DFI, OS, PFI, and DSS in some cancers. Additionally, GJB5 level was positively related to immune modulatory genes, TMB, immune cell infiltration, immunological checkpoints, and MSI in malignancies. Furthermore, our study demonstrated that GJB5 was upregulated in colorectal cancer tissues compared to normal tissues. We also assessed GJB5 expression across various pancreatic cell lines. Notably, GJB5 was highly expressed in pancreatic cancer cells relative to normal pancreatic epithelial cells. Additionally, GJB5 knockdown in pancreatic cancer cells resulted in a significant reduction in cell proliferation. In summary, the findings indicated the potential of GJB5 as a prospective prognostic indicator and immunological biomarker.
缝隙连接蛋白B5（GJB5，也称为连接蛋白31.1）最近有报道称在几种癌症类型中表达下调，在黑色素瘤和非小细胞肺癌（NSCLC）等癌症中它主要作为一种肿瘤抑制因子发挥作用。然而，尚无关于其在泛癌中的预后和免疫作用的报道。本研究通过全面的泛癌分析评估了GJB5在各种癌症类型中的相关性。比较了从癌症基因组图谱（TCGA）数据库获取的肿瘤组织和相邻组织中GJB5的差异表达。此外，进行了单因素Cox回归和Kaplan-Meier生存分析，以评估GJB5对各种癌症中疾病特异性生存（DSS）、无病间期（DFI）、临床分期、无进展间期（PFI）和总生存（OS）的影响。此外，通过肿瘤免疫单细胞中心（TISCH）评估了肿瘤微环境中GJB5的水平及其活性。此外，通过基因集富集分析进一步评估了GJB5水平在各种癌症中的生物学重要性。肿瘤-免疫系统相互作用数据库（TISIDB）和肿瘤免疫估计资源数据库2.0（TIMER2.0）工具表明，GJB5影响肿瘤的免疫浸润潜能。本研究还评估了GJB5与免疫特征的相关性：免疫调节基因、肿瘤突变负担（TMB）和微卫星不稳定性（MSI）。数据表明，在某些癌症中，GJB5水平升高与更差的DFI、OS、PFI和DSS相关。此外，在恶性肿瘤中，GJB5水平与免疫调节基因、TMB、免疫细胞浸润、免疫检查点和MSI呈正相关。此外，我们的研究表明，与正常组织相比，结直肠癌组织中GJB5上调。我们还评估了各种胰腺细胞系中GJB5的表达。值得注意的是，与正常胰腺上皮细胞相比，胰腺癌细胞中GJB5高表达。此外，胰腺癌细胞中GJB5敲低导致细胞增殖显著减少。总之，研究结果表明GJB5作为一种潜在的预后指标和免疫生物标志物的潜力。
