Impact of BSG/CD147 gene expression on diagnostic, prognostic and therapeutic strategies towards malignant cancers and possible susceptibility to SARS-CoV-2

Background BSG (CD147) is a member of the immunoglobulin superfamily that shows roles for potential prognostics and therapeutics for metastatic cancers and SARS-CoV-2 invasion for COVID-19. The susceptibility of malignant cancers to SARS-CoV-2 as well as the correlations between disease outcome and BSG expression in tumor tissues have not been studied in depth. Methods In this study, we explored the BSG expression profile, survival correlation, DNA methylation, mutation, diagnostics, prognostics, and tumor-infiltrating lymphocytes (TILs) from different types of cancer tissues with corresponding healthy tissues. In vitro studies for cordycepin (CD), N6-(2-hydroxyethyl) adenosine (HEA), N6, N6-dimethyladenosine (m(2)(6)A) and 5 & PRIME;-uridylic acid (UMP) on BSG expression were also conducted. Results We revealed that BSG is conserved among different species, and significantly upregulated in seven tumor types, including ACC, ESCA, KICH, LIHC, PAAD, SKCM and THYM, compared with matched normal tissues, highlighting the susceptibility of these cancer patients to SARS-CoV-2 invasion, COVID-19 severity and progression of malignant cancers. High expression in BSG was significantly correlated with a short OS in LGG, LIHC and OV patients, but a long OS in KIRP patients. Methylation statuses in the BSG promoter were significantly higher in BRCA, HNSC, KIRC, KIRP, LUSC, PAAD, and PRAD tumor tissues, but lower in READ. Four CpGs in the BSG genome were identified as potential DNA methylation biomarkers which could be used to predict malignant cancers from normal individuals. Furthermore, a total of 65 mutation types were found, in which SARC showed the highest mutation frequency (7.84%) and THYM the lowest (0.2%). Surprisingly, both for disease-free and progression-free survival in pan-cancers were significantly reduced after BSG mutations. Additionally, a correlation between BSG expression and immune lymphocytes of CD56bright natural killer cell, CD56dim natural killer cell and monocytes, MHC molecules of HLA-A, HLA-B, HLA-C and TAPBP, immunoinhibitor of PVR, PVRL2, and immunostimulators of TNFRSF14, TNFRSF18, TNFRSF25, and TNFSF9, was revealed in most cancer types. Moreover, BSG expression was downregulated by CD, HEA, m(2)(6)A or UMP in cancer cell lines, suggesting therapeutic potentials for interfering entry of SARS-CoV-2. Conclusions Altogether, our study highlights the values of targeting BSG for diagnostic, prognostic and therapeutic strategies to fight malignant cancers and COVID-19. Small molecules CD, HEA, m(2)(6)A and UMP imply therapeutic potentials in interfering with entry of SARS-CoV-2 and progression of malignant cancers.

Automated summary

This study investigated the expression profile and clinical significance of BSG in different types of cancer tissues. It revealed that BSG is upregulated in several tumor types and its expression is associated with susceptibility to SARS-CoV-2 invasion and the severity and progression of malignant cancers. Furthermore, BSG mutations were found to significantly affect survival in various cancers, and BSG expression was correlated with immune cell infiltration and immune-related factors. In addition, the study showed that small molecules CD, HEA, m(2)(6)A, and UMP have therapeutic potential for interfering with SARS-CoV-2 entry and cancer progression.