Nidogen-1: a candidate biomarker for ovarian serous cancer

Abstract

Effective biomarkers for early detection of ovarian cancer are needed. Our study previously showed that basement membrane protein, nidogen-1 plasma level was significantly increased in ovarian cancer patients. This study aimed to examine the plasma levels of nidogen-1 in a large patient population to evaluate its effectiveness in ovarian serous carcinoma and expression in tumor tissues. The concentration of nidogen-1 in circulating plasma specimens of 265 ovarian serous cancer patients and 98 healthy individuals were assayed by enzyme linked immunosorbent assay. The medical records of 265 ovarian serous cancer cases were reviewed retrospectively. The expression status of nidogen-1 in tumor tissues of 44 ovarian serous carcinoma patients was examined by immunohistochemical analysis. For statistical analysis, we used the Mann–Whitney U test, Fisher's exact test and receiver operating characteristic. Protein levels of nidogen-1 were considerably raised in the plasma from ovarian serous cancer patients compared with those in healthy controls (P < 0.001), especially elevated in patients with advanced stage and those received neoadjuvant chemotherapy followed by interval debulking surgery. However, it was irrelevant to the grade, chemotherapy sensitivity or residual tumor of the ovarian serous carcinoma cases investigated (P > 0.05). Receiver operating characteristic curve analysis for nidogen-1 showed that it could discriminate patients with ovarian serous carcinomas from healthy controls [areas under the curve (AUC): 0. 65, 95%CI, 0.59–0.71], but CA125 was superior (AUC: 0. 98, 95%CI, 0.96–0.99). The immunohistochemical staining result showed that nidogen-1 protein was localized both in the cancer cell cytoplasm and intercellular substance, mainly expressed in extracellular matrix of ovarian serous carcinoma tissues (the positive rate was 77.3%). Our study suggests that plasma nidogen-1 may be used as a diagnostic biomarker for ovarian serous carcinoma and can reflect the tumor burden.