Association of WHSC1/NSD2 and T-cell infiltration with prostate cancer metastasis and prognosis.

Progress in immunotherapy for prostate cancer (PCa) lags that for other cancers, mainly because of limited immune infiltration in PCa. This study aimed to assess the feasibility of NSD2 as an immunotherapeutic target in PCa. Immunohistochemistry was performed to evaluate the expression pattern of NSD2 in 34 cases of benign prostatic hyperplasia (BPH), 36 cases of prostatic intraepithelial neoplasia (PIN), and 57 cases of PCa, including 19 cases of metastatic castration-resistant prostatic cancer (mCRPC). Single-cell RNA sequencing and gene set enrichment analysis (GSEA) were used to correlate NSD2 with certain downstream pathways. Furthermore, the Immuno-Oncology-Biological-Research (IOBR) software package was used to analyze the potential roles of NSD2 in the tumor microenvironment. We found that the positive expression rate of NSD2 increased progressively in BPH, PIN and PCa. mCRPC had the highest staining intensity for NSD2. High NSD2 expression was positively correlated with the infiltration level of CD4+ tumor-infiltrating lymphocytes (TILs) and negatively correlated with that of CD8+ TILs. Importantly, a new immune classification based on NSD2 expression and CD4+ TILs and CD8+ TILs was successfully used to stratify PCa patients based on OS.PSA and CD4+ TILs are independent risk factors for PCa bone metastasis. This study demonstrates a novel role for NSD2 in defining immune infiltrate on in PCa and highlights the great potential for its application in immunotherapy response evaluation for prostate malignancies.