The Oncogenic Role of Prostate Stem Cell Antigen (PSCA) in Colorectal Cancer: Implications for Targeted Therapy

Prostate stem cell antigen (PSCA), a pivotal member of the lymphocyte antigen-6 (Ly6) protein family, has been implicated in the tumorigenesis and neoplastic progression of diverse cancer types. In this study, we conducted a thorough investigation into the role of PSCA in the development of colorectal cancer (CRC). Survival analysis based on The Cancer Genome Atlas (TCGA) dataset demonstrated that elevated expression of PSCA was tightly correlated with unfavorable overall survival, inferior relapse-free survival and worse post-progression survival among CRC patients.Additionally, PSCA exhibited significantly higher expression levels in colorectal cancer stem cell (CRC-SCs) rel-ative to CRC cell lines.Loss-of-function assaysusing small interfering RNA (siRNA)-mediated silencing were performed to evaluate the effects of PSCA downregula-tion on the stemness properties of CRC-SCs, including proliferative capacity, invasive potential and apoptotic rate, which were assessed by MTS assay, transwell invasion assay and flow cytometry analysis, respectively. The results showed that silencing PSCA markedly suppressed the proliferation and invasion of CRC-SCs, while significantly promoting cellular apoptosis. RNA sequencing was performed to identify differentially expressed genes (DEGs) in the PSCA knockdown group compared to the negative control group.