SOGA1蛋白表达对晚期高级别浆液性卵巢癌PARP抑制剂一线维持治疗疗效的预测价值OA

Objective:To investigate the predictive value of suppressor of glucose and autophagy associated 1(SOGA1)protein expression for therapeutic efficacy of first-line poly(ADP-ribose)polymerase(PARP)inhibitor maintenance therapy in patients with advanced high-grade serous carcinoma(HGSC).Methods:Patients with advanced HGSC who received first-line maintenance therapy with a PARP inhibitor(olaparib,niraparib,or fluzoparib)were retrospectively enrolled.Ad-ditionally,42 normal ovarian tissue samples resected for benign conditions were enrolled as controls,along with paired tumor specimens from 13 patients with platinum-sensitive recurrent HGSC,including both treatment-naïve primary tumors and re-current tumors resected after PARP inhibitor therapy.SOGA1 protein expression in tumor tissues was detected via immuno-histochemistry.X-tile software was used to calculate the optimal cutoff value of SOGA1 expression according to progression-free survival(PFS)data.The expression levels of SOGA1 were compared between HGSC tissues and normal ovarian tissues,as well as between paired primary and recurrent tumor specimens.The association between SOGA1 expression and clinico-pathological characteristics as well as PFS was analyzed.Univariate and multivariate analyses were performed using Cox pro-portional hazards regression models.Results:In the 160 patients with advanced HGSC receiving first-line PARP inhibitor maintenance therapy in this study,high SOGA1 expression was significantly associated with more advanced FIGO stage,low-er R0 resection rate,lower BRCA1/2 or homologous recombination deficiency positivity rate,poorer response to first-line chemotherapy,and higher CA125 levels before maintenance therapy(all P<0.05).Survival analysis revealed that patients with high SOGA1 expression had significantly shorter PFS than those with low expression(P<0.001).Multivariate Cox a-nalysis indicated that high SOGA1 expression was an independent risk factor for shortened PFS(HR=1.92,95%CI:1.25～2.96,P<0.01).Furthermore,SOGA1 expression was significantly higher in HGSC tissues compared with 42 nor-mal ovarian tissue controls(P<0.001).In paired specimens from 13 patients who experienced recurrence after PARP in-hibitor therapy,the expression level of SOGA1 in recurrent tumor tissues was significantly higher than that in the matched treatment-naïve primary tumor tissues(P=0.003).Validation using the HPA database,which includes patients with ovari-an cancer not treated with PARP inhibitors,suggested that high SOGA1 expression was associated with poor overall survival.Conclusion:High SOGA1 protein expression is an independent risk factor for shortened PFS in patients with advanced HGSC receiving first-line PARP inhibitor maintenance therapy,suggesting its potential as a predictive molecular biomarker for PARP inhibitor efficacy.