Higher expression of calcineurin predicts poor prognosis in unique subtype of ovarian cancer

Abstract

Background: The role of calcineurin/NFAT signaling in ovarian cancer has been unknown. NFAT was significantly overexpressed in ovarian cancer tissues and that overexpression of NFAT was significantly associated with metastasis and poor prognosis on clinical tissue level. To investigate whether NFAT upstream protein, calcineurin (CN), affects the prognosis in various histological subtype of ovarian cancer (OC).

Methods: The association between CN and clinical features was analyzed in 50 OC patients treated from 2007 to 2012. CN expression was examined using immunohistochemistry. We observed the association of CN expression with the prognosis in these patients.

Results: CN expression was significantly increased in later-stage tumor tissue of serous carcinoma compared with those with early-stage. The expression of CN positively correlated with the serum cancer antigen 125 (CA125) level in ovarian clear-cell carcinoma and the serum alpha-fetoprotein (AFP) level in papillary serous cystadenocarcinoma. Particularly, higher CN expression in tumor tissues significantly correlated with reduced overall survival among patients with serous carcinoma. In addition, the serum cancer antigen 72-4 (CA72-4) level, serum carcinoembryonic antigen (CEA) levels, pathological stage, lymph node metastasis, and chemotherapeutic resistance were identified as significant prognostic factors in ovarian clear-cell carcinoma, serous carcinoma, or papillary serous cystadenocarcinoma.

Conclusions: CN is upregulated in ovarian cancer tissues with later-stage and that the expression of CN, CA72-4, and CEA was remarkably associated with poor prognosis in unique subtype of ovarian cancer. CN levels may be investigated for use as a prognostic biomarker for risk assessment in unique subtype of OC patients.

Keywords: Calcineurin; Cancer antigen 72–4; Carcinoembryonic antigen; Histological subtype; Ovarian cancer; Prognosis.

Fig. 1

Immunohistochemical staining for CN in ovarian cancer. The tumor tissues of ovarian cancer patients were analyzed for CN expression by immunohistochemical staining as described in Methods. CN(−) indicated the CN-negative expression; CN(+) indicated the CN-positive expression. Scale bar: 50 μm

Fig. 2

The expression of the CN in ovarian cancer with later-stage or early-stage. The different subtypes of human ovarian cancer, including (a) total type, (b) clear cell carcinoma, (c) serous carcinoma, and (d) papillary serous cystadenocarcinoma, were examined the expression of CN via IHC staining (CN-positive percentage). The results were presented as the percentage-change in CN expression of later-stage tumor tissue (stage III~IV) relative to that in early-stage tumor tissue (stage I~II). The CN expression of serous carcinoma was significantly higher in later-stage tumor tissue than in early-stage tumor tissue (p < 0.05)

Fig. 3

The expression of the CN in ovarian cancer with large or small tumor sizes. The different subtypes of human ovarian cancer, including (a) total type (b) clear cell carcinoma, (c) serous carcinoma, and (d) papillary serous cystadenocarcinoma, were examined the CN expression via IHC staining (CN-positive percentage). The results were presented as the percentage-change in CN expression of large tumor size (≧395 mm3) relative to that in small tumor size (< 395 mm3). The CN expression of clear-cell carcinoma, serous carcinoma, or papillary serous cystadenocarcinoma was higher in large tumor size than in small tumor size, but was not statistically significantly (p > 0.05)

Fig. 4

Association of CN expression with disease-free survival in ovarian cancer. The different subtypes of human ovarian cancer, including (a) total type, (b) clear cell carcinoma, (c) serous carcinoma, and (d) papillary serous cystadenocarcinoma, were examined the expression of CN via IHC staining (CN-positive percentage). Kaplan-Meier curve presenting the disease-free survival of ovarian cancer exhibiting high or low CN expression. Higher CN expression level (expression level > 50% positive percentage) in tumor tissues of each subtype was not significantly associated with reduced disease-free survival (p > 0.05)

Fig. 5

Association of CN expression with overall survival in ovarian cancer. The different subtypes of human ovarian cancer, including (a) total type, (b) clear cell carcinoma, (c) serous carcinoma, and (d) papillary serous cystadenocarcinoma, were examined the expression of CN via IHC staining (CN-positive percentage). Kaplan-Meier curve presenting the overall survival of ovarian cancer exhibiting high or low CN expression. Higher CN expression level (expression level > 50% positive percentage) in tumor tissues of serous carcinoma was significantly associated with reduced overall survival (p < 0.05)