CD276 (B7-H3) expression in prostate cancer: associations with clinicopathological, immune-related, and neuroendocrine-associated features

CD276 (B7-H3) is highly expressed in various malignancies; however, its clinical significance and associations with immune-related and neuroendocrine-associated features in prostate cancer (PCa) remain incompletely understood. This study aimed to characterize CD276 expression and investigate its associations with clinicopathological characteristics, immune-related parameters, and neuroendocrine-associated markers in a Chinese prostate cancer cohort. A total of 364 patients who underwent radical prostatectomy at our center between January 2023 and September 2024 were enrolled. Immunohistochemistry was performed to evaluate CD276 and related marker expression, and serum cytokine profiles were analyzed. Associations between CD276 expression and clinicopathological parameters, immune-related factors, and neuroendocrine-associated markers were assessed using statistical analyses. Because longitudinal follow-up data were unavailable for the institutional cohort, survival analyses were conducted using publicly available external datasets to explore the potential prognostic relevance of CD276. In unadjusted analyses, high CD276 expression was associated with Gleason score ≥ 7 ( P = 0.030), pT3–T4 disease ( P = 0.022), distant metastasis ( P = 0.025), Ki-67 ≥ 5% ( P = 0.023), and PSA > 5 ng/mL ( P = 0.024), although continuous PSA levels did not differ significantly between the CD276-high and CD276-low groups. After multivariable adjustment, statistical evidence remained for the associations of high CD276 expression with pT3–T4 disease (aOR, 2.06; 95% CI, 1.25–3.40; P = 0.005) and M1 disease (aOR, 2.43; 95% CI, 1.19–4.95; P = 0.015), whereas the associations with PSA > 5 ng/mL and Gleason score ≥ 7 were attenuated. Exploratory analyses of external datasets further showed associations between higher CD276 expression and poorer survival outcomes in prostate cancer-related cohorts and an anti-PD-1-treated pan-cancer cohort. Regarding immune-related features, high CD276 expression was associated with a higher frequency of absent detectable CD3⁺ lymphocyte infiltration ( P = 0.034), higher serum IL-12p70 levels ( P = 0.045), and lower serum IL-10 ( P = 0.047), IFN-γ ( P = 0.046), and IFN-α (P = 0.047) levels. Regarding neuroendocrine-associated features, CD276 expression was positively associated with synaptophysin (SYN, P = 0.048), neuron-specific enolase (NSE, P < 0.001), chromogranin A (CgA, P = 0.033), and PTEN protein loss ( P = 0.037). CD276 expression was associated with aggressive clinicopathological characteristics in the institutional cohort, while exploratory analyses of external datasets showed associations between higher CD276 expression and poorer survival outcomes. Given the differences between the external datasets and the institutional cohort, these findings do not establish CD276 as an independent prognostic biomarker in surgically treated prostate cancer and require prospective validation in a clinically matched cohort. Its associations with immune-related parameters and neuroendocrine-associated markers further suggest that higher CD276 expression may characterize a distinct biological phenotype in prostate cancer. However, these findings are based on retrospective correlative analyses, and further prospective studies and functional investigations are required to determine their biological and clinical significance.