Table6_Pan-Cancer Analysis, Reveals COVID-19-Related BSG as a Novel Marker for Treatment and Identification of Multiple Human Cancers.xlsx

Background: Coronavirus disease 2019 (COVID-19) has been a public threat and healthcare concern caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. During the period of the pandemic of COVID-19, cancer patients should be paid more attention as more severe events are found in cancer patients infected with SARS-CoV-2. Basigin (BSG) is an essential factor for the infection and progression of COVID-19 and tumorigenesis of multiple tumors, which may serve as a novel target for the effective treatment against COVID-19 and multiple human cancers.
Methods: A total of 19,020 samples from multiple centers were included in our research for the comprehensive investigation of the differences in BSG expression among human organs, cancer cells, cancer tissues, and normal tissues. Cox regression analysis and Kaplan–Meier curves were utilized to explore the prognosis factor of BSG in cancers. Correlation analyses were used to determine associations of BSG expression with tumor mutational burden, the immune microenvironment, etc. Gene set enrichment analysis was applied to explore the underlying mechanisms of BSG in cancers.
Results: Compared with normal tissues, BSG expression was high in 13 types of cancers (cholangiocarcinoma, etc.) and low in colon adenocarcinoma and rectum adenocarcinoma. BSG expression was related to the prognosis of eight cancers (e.g., invasive breast carcinoma) (p < 0.05). The gene also demonstrated a pronounced effect in identifying 12 cancers (cholangiocarcinoma, etc.) from their control samples (AUC >0.7). The BSG expression was associated with DNA methyltransferases, mismatch repair genes, immune infiltration levels, tumor mutational burden, microsatellite instability, neoantigen, and immune checkpoints, suggesting the potential of BSG as an exciting target for cancer treatment. BSG may play its role in several cancers by affecting several signaling pathways such as drug cytochrome metabolism P450 and JAK-STAT.
Conclusion:BSG may be a novel biomarker for treating and identifying multiple human cancers.

背景：新型冠状病毒肺炎（Coronavirus disease 2019, COVID-19）是由严重急性呼吸综合征冠状病毒2型（severe acute respiratory syndrome coronavirus 2, SARS-CoV-2）感染引发的公共卫生威胁与医疗健康难题。在COVID-19大流行期间，癌症患者需得到更多关注，因为感染SARS-CoV-2的癌症患者往往会出现更严重的不良事件。嗜碱性蛋白（Basigin, BSG）是COVID-19感染与进展、以及多种肿瘤发生发展的关键因子，有望成为抗击COVID-19与多种人类癌症的新型治疗靶点。
方法：本研究纳入多中心来源的19020例样本，旨在全面探究BSG在人体器官、癌细胞、癌组织及正常组织中的表达差异。采用Cox回归分析与Kaplan-Meier曲线，探索BSG在癌症中的预后价值；通过相关性分析明确BSG表达与肿瘤突变负荷、免疫微环境等指标的关联；运用基因集富集分析（Gene Set Enrichment Analysis, GSEA）揭示BSG在癌症中发挥作用的潜在分子机制。
结果：与正常组织相比，BSG在13种癌症（如胆管癌等）中呈高表达，在结肠腺癌与直肠腺癌中呈低表达。BSG表达与8种癌症（如浸润性乳腺癌等）的预后显著相关（P<0.05）。该基因还可有效区分12种癌症（如胆管癌等）与其对照样本（曲线下面积Area Under Curve, AUC>0.7）。BSG表达与DNA甲基转移酶、错配修复基因、免疫浸润水平、肿瘤突变负荷、微卫星不稳定性、新抗原及免疫检查点均存在显著关联，提示BSG有望成为极具潜力的癌症治疗靶点。BSG可能通过调控细胞色素P450药物代谢通路、JAK-STAT等多条信号通路，在多种癌症中发挥生物学功能。
结论：BSG有望成为一种全新的、可用于多种人类癌症诊疗的生物标志物。