Proteomic profiling identifies circulating soluble MCAM/CD146 as a candidate biomarker for abnormal semen parameters in male infertility

Background: A growing body of evidence suggests that male infertility is a precursor to future health problems. This study aimed to develop a unique circulating biomarker that could contribute to the diagnosis of male infertility. Materials and methods: The study included 114 adult male participants aged 20–50 years who underwent sperm collection for in vitro fertilization and embryo transfer at Nagoya University Hospital, Gifu University Hospital, and Misao Ladies Hospital. Results: Circulating VEGF-A and sFlt-1 levels did not differ significantly between men with normal and abnormal semen parameters. In contrast, proteomic analysis identified VEGFR1/2-related proteins associated with sperm motility, among which soluble MCAM/CD146 was significantly elevated in participants with abnormal semen parameters (84.0 [20.9–183.8] pg/mL vs 352.7 [115.8–1236.3] pg/mL, p<0.0001), and in similar those with reduced sperm motility (106.5 [25.1–282.6] pg/mL vs 352.7 [125.5–1133.4] pg/mL, p<0.0001). Receiver operating characteristic analysis demonstrated the diagnostic potential of soluble MCAM/CD146, with an area under the curve of 0.787, 66.7% sensitivity, and 78.6% specificity at the optimal threshold, supporting its role as a candidate biomarker for male infertility. Conclusions: Circulating soluble MCAM/CD146 may represent a potential biomarker associated with abnormal semen parameters.