A Systematic Immune and Prognostic Analysis of CD48 Interaction with Tumor Microenvironment in Pan-Cancer

The cluster of differentiation 48 (CD48) is a member of the signaling lymphocyte activation molecule family, constitutively expressed on most hematopoietic cells. CD48 was reported to affect immune regulation in certain tumors, thereby influencing tumor development and prognosis, but its impact on the prognosis and immune infiltration in pan-cancer remains unclear.

We systematically analyzed the raw data from The Cancer Genome Atlas (TCGA), Tumor Immune Estimation Resource (TIMER), and Tumor Immune Dysfunction and Exclusion (TIDE) databases. Initially, we investigated the differences in CD48 expression between pan-cancer and adjacent normal tissues. Then, the correlation analysis of CD48 with tumor mutational burden (TMB), microsatellite instability (MSI), tumor microenvironment (TME), and immune-related genes was evaluated. Moreover, bioinformatics tools: ESTIMATE and gene set enrichment analysis (GSEA) were used for tumor immunology analysis in pan-cancer. We performed validation studies including quantitative real-time PCR (qPCR) and Western blotting.

Differential analysis revealed that CD48 was significantly altered in pan-cancer as compared with normal tissues. Meanwhile, the survival analysis demonstrated that CD48 strongly correlated with overall survival (OS), disease-free interval (DFI), progression-free interval (PFI), and disease-specific survival (DSS), indicating its crucial role in the tumor patients' prognosis. CD48 expression was also associated with TMB and MSI levels in 17 and 14 types of pan-cancers, respectively. Moreover, CD48 was linked to immune infiltrating cells and stromal components in the TME.

Concludingly, patients with pan-cancer may benefit from evaluating CD48 as a prognostic and immunotherapy response biomarker.