NFAT Overexpression Correlates with CA72-4 and Poor Prognosis of Ovarian Clear-Cell Carcinoma Subtype.

Abstract

Current biomarkers did not overcome the limitations of clinical application due to the heterogeneity of ovarian tumors. The role of nuclear factor of activated T cells (NFAT) in the prognosis of different histological subtypes of ovarian cancer remains unclear. NFAT expression was analyzed in 302 ovarian tumors from The Cancer Genome Atlas (TCGA) dataset and was further confirmed by 88 ovarian tumor specimens, including 30 clear-cell carcinoma, 34 serous carcinoma, and 24 papillary serous cystadenocarcinoma. The correlations between NFAT expression, cancer biomarkers, and clinical characteristics in different subtypes of ovarian tumors were analyzed. ALGGEN PROMO, reporter assay, and NFAT overexpression and knockdown were used to identify chondroadherin (CHAD) as the downstream target of NFAT. NFAT was significantly upregulated only in late-stage clear-cell carcinoma, but not in other two subtypes. NFAT levels were correlated with CA72-4 levels and poor overall survival and disease-free survival (P < 0.05), suggesting that NFAT together with CA72-4 were specific prognostic markers for clear-cell carcinoma. Pathological stage and lymph node metastasis were the prognostic factors affecting serous carcinoma (P < 0.05), while CA-125 was the prognostic factor affecting papillary serous cystadenocarcinoma (P < 0.05). PROMO and reporter assay indicated that CHAD was the downstream target of NFAT. In addition, NFAT overexpression and silencing increased and reduced CHAD expression, respectively. NFAT together with CA72-4 were specific tumor markers for risk assessment of unique clear-cell subtype of ovarian tumors. CHAD was identified as the downstream target gene of NAFT and was associated with poor survival of ovarian cancer.