1. Department of Gynecologic Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510080, China.
2. Department of Molecular Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA
3. Department of Biology, University of Illinois at Chicago, Chicago, IL 60607, USA
4. Department of Forensic Medicine, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China
# These authors contributed equally to this work and share first authorship.
Objective: Golgi phosphoprotein 3 (GOLPH3) is a highly conserved membrane protein that is involved in a variety of cancers such as colorectal cancer, gastric cancer, ovarian cancer, and breast cancer. GOLPH3L is a paralog of GOLPH3. Although these proteins share a similar amino acid sequence, much less is known regarding the subcellular functions or effects of GOLPH3L on cancer compared with GOLPH3. The role of GOLPH3L in epithelial ovarian cancer (EOC) has not yet been investigated.
Methods: Using western blot, PCR and immunohistochemical analyses, we studied the clinical significance of GOLPH3L expression in EOC. The correlations between GOLPH3L expression and the clinicopathological variables of patients with EOC were assessed using Pearson's χ2 test. Kaplan-Meier analysis was used to compare the postoperative survival between groups of patients with EOC with varying levels of GOLPH3L expression.
Results: High expression of GOLPH3L was more frequently observed in EOC tissues than in corresponding adjacent non-tumor tissues. The expression of GOLPH3L correlated closely with pre-operative CA125 level (P=0.031). Univariate analysis showed that age, FIGO stage, pre-operative cancer antigen (CA) 125, pre-operative albumin concentration (AC), optimal cytoreductive surgery (CRS) and GOLPH3L expression correlate significantly with overall survival (OS). Multivariate analysis revealed that GOLPH3L expression was an independent prognostic factor for OS of patients with EOC (102 months versus 72 months; P=0.013). What's more, knocked down of GOLPH3L with small interfering RNA (siRNA) technology of OVCAR3 and SKOV3 cell lines reduced cell viability obviously, compared to the negative control and blank control groups.
Conclusions: Our data show that increased expression of GOLPH3L is associated with poor prognosis of patients with EOC and may act as a novel, useful and independent prognostic indicator. Therefore, further studies are warranted.
Keywords: GOLPH3L, epithelial ovarian cancer, prognosis