Stonin 2 Overexpression is Correlated with Unfavorable Prognosis and Tumor Invasion in Epithelial Ovarian Cancer.

Xiaoying Sun,Yanna Zhang,Chunhao Niu,Weijing Zhang,Yulan Ou,Han Li,Libing Song

doi:10.3390/ijms18081653

Abstract

Stonin 2 (STON2), which functions in adjusting endocytotic complexes, is probably involved in the monitoring of the internalization of dopamine D2 receptors which have an inhibitory action of dopamine on tumor progression. However, its clinical significance in tumor progression and prognosis remains unclear. We explored the association between STON2 and the clinicopathological characteristics of epithelial ovarian cancer (EOC). The STON2 levels in ovarian cancer and normal cell lines and tissues were detected by real-time PCR and Western blot analyses. STON2 protein expression was also detected by an immunohistochemical analysis. The clinical significance of STON2 expression in ovarian cancer was statistically analyzed. STON2 significantly increased in the ovarian cancer cell lines and tissues compared to the normal ones. In the 89 EOC samples tested, STON2 expression was significantly correlated with intraperitoneal metastasis, intestinal metastasis, intraperitoneal recurrence, ascites containing tumor cells, and CA153 level. Moreover, patients with STON2 protein overexpression were more likely to exhibit platinum resistance and to have undergone neoadjuvant chemotherapy. Patients with high STON2 protein expression had a tendency to have a shorter overall survival and a poor prognosis. A multivariate analysis showed that STON2 was an independent prognostic predictor for EOC patients. In conclusion, STON2 plays an important role in the progression and prognosis of ovarian carcinoma, especially in platinum resistance, intraperitoneal metastasis, and recurrence. STON2 can be a novel antitumor drug target and biomarker which predicts an unfavorable prognosis for EOC patients.

Highlights

Ovarian cancer is the leading cause of death from gynecologic malignancy, and is associated with an incidence of approximately 22,280 new cases and an annual mortality rate of 14,240 deaths in the United States in 2016 [1]
Ovarian tumor treatments have been improving over the past few decades in particular, recent studies have explored platinum-containing chemotherapeutic agents as well as neoadjuvant chemotherapy (NAC) [2]
Considering the high expression of Stonin 2 (STON2) in ovarian cancer, we further investigated its correlation with the clinical characteristics of ovarian cancer in 89 cases by immunohistochemistry

Summary

Introduction

Ovarian cancer is the leading cause of death from gynecologic malignancy, and is associated with an incidence of approximately 22,280 new cases and an annual mortality rate of 14,240 deaths in the United States in 2016 [1]. Ovarian tumor treatments have been improving over the past few decades in particular, recent studies have explored platinum-containing chemotherapeutic agents as well as neoadjuvant chemotherapy (NAC) [2]. Regardless of these advances, ovarian cancer remains one of the deadliest types of gynecological carcinomas, of which the 5-year survival rate is merely 20–40%, primarily due to the occurrence of tumor metastasis and recurrence [3]. Further studies to identify reliable novel factorsIntt.hJ.aMtolc. aScni. 2a01i7d, 18i,n165t3he detection of tumor metastasis, predict tumor recurren ocfe14and survival, and provide personalized prediction for targeted therapy are essential in the prevention of tumor recurrence anwOdbitshtfeoetarrricliysm-(sFtpaIGgreoO,v)loIicInIagloizrteIhdVeo),vplaerraiodaingnncgaotnosceiasrdwoisefarpeppraeotpiinoetrintnetgdsptworohgiatnvhoesEaisnO[a4Cv,5e].r.aOgne the other hand, patients five-year survival rate of

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