Contemplating the prognostic and therapeutic potential of CD19: a comprehensive analysis across diverse cancer types.

BACKGROUND

Cancer represents a highly intricate disease, characterized by the uncontrolled proliferation and invasion of aberrant cells, leading to widespread global morbidity and mortality. This study investigates the influence of CD19, a marker specific to B-cells, within the tumor microenvironment (TME) across a spectrum of cancer types.

METHODOLOGY

To explore the role of CD19, we employed a wide array of bioinformatics tools and databases, including UALCAN, GEPIA2, univariate Cox regression, KM plotter, HPA, GSCA, cBioPortal, TISIDB, and DAVID. Additionally, we conducted experimental validations using cell culture, Real-time quantitative PCR (RT-qPCR), and western blot analyses.

RESULTS

An extensive analysis of CD19 expression was performed using The Cancer Genome Atlas (TCGA) data sourced from TIMER2 and UALCAN, covering 33 different cancer types. We observed a marked variability in CD19 expression, with notable upregulation in Adrenocortical Carcinoma (ACC) and Breast Invasive Carcinoma (BRCA), contrasted by significant downregulation in Cervical Squamous Cell Carcinoma (CESC), Rectum Adenocarcinoma (READ), and Sarcoma (SARC). Prognostic assessments through univariate Cox regression and Kaplan-Meier plots revealed that lower levels of CD19 were linked to a poorer overall survival rate in CESC, READ, and SARC. These findings were reinforced by validation using GEPIA2 and GSCA, where reduced CD19 expression correlated negatively with methylation levels in the affected cancers. Furthermore, immunohistochemical staining data from the Human Protein Atlas (HPA) provided additional confirmation of these results. Mutation analysis through cBioPortal suggested that alterations in CD19 were infrequent and had a minimal impact on tumor mutation burden (TMB) and microsatellite instability (MSI). Correlation studies using TISIDB highlighted significant associations between CD19 expression and immune-related genes, emphasizing its potential role in immune regulation. Additionally, GSCA analysis demonstrated that CD19 expression was positively associated with immune cell infiltration, though no significant effect on drug sensitivity was detected. Experimental validation using RT-qPCR in READ cell lines substantiated the down-regulation of CD19. Further functional analysis revealed that reduced CD19 expression significantly influenced the cellular behavior of SW480 cells.

CONCLUSION

These findings underscore the critical role of CD19 within the tumor microenvironment, suggesting its potential as a biomarker and a therapeutic target in specific types of cancer.