JCHAIN: A Prognostic Marker Based on Pan-Cancer Analysis to Inhibit Breast Cancer Progression

The JCHAIN (immunoglobulin-linked chain) is a multimeric IgA and IgM-linked chain whose involvement in oncogenesis and immunomodulation is unknown. The goal of this work was to conduct a comprehensive pan-cancer analysis of the JCHAIN to determine its expression profile, prognostic significance, immune infiltration, and function in diverse malignancies.

We performed pan-cancer analysis of gene expression data and protein expression data of JCHAIN using multiple databases, and analysed the prognostic significance of JCHAIN in a variety of cancers using univariate Cox analysis and Kaplan-Meier tools. The relationship between JCHAIN and immune cell infiltration was analysed via the TISIDB and TIMER websites, while single-cell and spatial transcriptomic analyses were performed to analyse the relationship between JCHAIN and the immune microenvironment. Mutations in the JCHAIN and their connection with methylation were then investigated using the cBioPortal and UALCAN websites. Afterwards, the function of JCHAIN was analysed by KEGG as well as GSEA, and the function of JCHAIN in breast cancer cells was verified by in vitro experiments.

The expression of the JCHAIN gene shows significant differences in most cancers, and its high expression is associated with a favourable prognosis. In most cancers, JCHAIN gene expression is closely linked to immune-related genes, immune cells, and methylation, as well as to being affected by mutations. In breast cancer, we found that the JCHAIN was negatively correlated with cellular stemness. Enrichment analysis indicated that the JCHAIN was involved in immune responses, B cell activation, and JAK-STAT signalling pathways. Functional experiments showed that overexpression of the JCHAIN inhibited tumour migration and invasion, which may be closely related to the activation of the IL-2/STAT4 signalling pathway.

We found that JCHAIN can be used as a diagnostic and prognostic marker for a variety of cancers by pan-cancer analysis and verified that JCHAIN affects breast cancer cell progression through IL-2/STAT4 by in vitro experiments.