Clinical Value Of GRK5/ACTC1 Co-overexpression In Epithelial Ovarian Cancer

Background and ObjectiveOvarian cancer(OC)is the leading cause of mortality among female reproductive malignant cancers in China,and it is the second most common cause of gynecologic cancer-related death in women worldwide.Gloably,there are 239,000 new cases and 152,000 deaths every year,making ovarian cancer the seventh most common cancer and the second most common cause of gynecologic cancer-related mortality.And the most type isepithelial ovarian cancer(EOC).Despite cytoreduction and combination chemotherapies were performed to treat ovarian cancer,but the prognosis remains poor.Recently several tumor biomarkers have been used to monitor the progression and predict prognosis of EOC,butthese biomarkers are not very accurate.Therefore,to construct the new prognostic predicting model and to provide precise or individual therapy are very important.GRK5 is one of the G protein-coupled receptor kinase(GRK)family members.It can regulate GPCR signaling,which correlates with various diseases like cardiac dysfunction,diabetes,hypertension,Alzheimer’s disease and cancers.And it functions as oncogenes in glioblastoma,prostatel,pancreas,non-small-cell lung and breast cancers.Similar to GRK5,ACTC1 is also a cardiac-related gene.It encodes cardiac actin and amutation at c.G301A causes hypertrophic cardiomyopathy,and,in some cases,sudden cardiac death.Recently some reports have demonstrated that ACTCI plays an important role in human colon cancer,oral squamous cell carcinoma,glioblastoma,and so on.However,the role of ACTC1 in EOC has never been reported,and the relationship between GRK5 and ACTC1 and EOC has never been explored yet.Therefore,the present study aimed to explore the exact role of GRK5 and ACTC1 in EOC by examining its expression in tisues and paratumor tissues(both paraffin-embeddedand fresh samples),determining the association of GRK5 and ACTC1 and their coexpression with clinicopathological parameters and assessing the prognostic value in EOC.MethodsA total of 172 paraffin-embedded cancer tissues of EOC patients diagnosed and operated at the memorial hospital of Sun Yat-sen University Between December 2009 and March 2017 and 41paratumor tissues were collected and assessed for GRK5 and ACTC1 expression using immunohistochemistry(IHC),respectively.Furthermore,16 fresh EOC tissues and their matched paratumor tissues were collected from the Integrated Hospital of Traditional Chinese Medicine,Southern Medical University,between August 2013 and November 2019 and subjected to reverse-transcription quantitative PCR(RT-qPCR)analysis to detect the mRNA expression of GRK5 and ACTC1,respectively.ResultsThe expression of GRK5 and ACTC1 was both higher in cancer tissues than in paratumor tissues.GRK5 expression was positively correlated with ACTC1 expression.In addition,GRK5,ACTC1 and GRK5/ACTC1 expression was associated with recurrence-free survival(RFS)and overall survival(OS)in EOC patients.Furthermore,multivariate logistic regression analysis indicated that GRK5+/ACTC1+coexpression was an indeed independent predictor of poor survival inpatients with EOC.ConclusionGRK5 and ACTC1 may both play oncogenic role in EOC,and co-expression of GRK5+/ACTC1+can be recommended as prognostic predicting biomarkers in EOC,and it may provide important value in clinical therapy and supervision of EOC.