背景:关于同源重组修复(HRR)基因组中包含的特定基因对于鉴定HRR缺陷(HRD)状态和预测上皮性卵巢癌(EOC)患者的预后尚无共识。
目的:我们旨在探索涉及HRR通路的15个基因组作为中国新诊断为EOC患者的预测预后指标。
方法:我们回顾了以前发表的关于不同HRR基因组的报道,并预先指定了15个基因组。收集了来自六个中心的2014年至2022年诊断的308名EOC患者的15个基因小组的基因检测结果。临床病理特征的关联,我们评估了聚(二磷酸腺苷-核糖)聚合酶抑制剂(PARPis)的使用和15个基因组HRR突变(HRRm)状态的无进展生存期(PFS).
结果:43.2%(133/308)的患者被确定为携带144个有害HRRm,其中68.1%(98/144)为种系突变,32.8%(101/308)为BRCA1/2基因致死突变。风险比(HR)(95%置信区间,CI)用于PFS(HRRmvHRR野生型,使用15个基因组的HRRwt)在所有阶段的HRRm为0.42(0.28-0.64),在IIIC-IV阶段为0.42(0.27-0.65)。然而,仅在BRCA突变组和HRRwt组之间观察到预后差异,非BRCAHRRm组和HRRwt组之间不存在。对于未使用PARPis的患者亚组,在IIIC-IV阶段,HR(95%CI)为0.41(0.24-0.68)。
结论:这项研究提供了证据,表明15基因组HRRm可以预测EOC的预后,其中只有BRCA1/2突变,不是非BRCAHRRm,有助于预后预测。在没有PARPis的患者中,HRRm组PFS较好。这是首次在中国人群中进行此类研究。
BACKGROUND: There is no consensus regarding the specific genes included in the homologous recombination repair (HRR) gene panel for identifying the HRR deficiency (HRD) status and predicting the prognosis of epithelial ovarian cancer (EOC) patients.
OBJECTIVE: We aimed to explore a 15-gene panel involving the HRR pathway as a predictive prognostic indicator in Chinese patients newly diagnosed with EOC.
METHODS: We reviewed the previously published reports about different HRR gene panels and prespecified the 15-gene panel. The genetic testing results in a 15-gene panel from 308 EOC patients diagnosed between 2014 and 2022 from six centers were collected. The association of clinicopathologic characteristics, the use of poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPis) and progression-free survival (PFS) with 15-gene panel HRR mutations (HRRm) status was assessed.
RESULTS: 43.2% (133/308) of patients were determined to carry 144 deleterious HRRm, among which 68.1% (98/144) were germline mutations and 32.8% (101/308) were BRCA1/2 gene lethal mutations. The hazard ratio (HR) (95% confidence interval, CI) for PFS (HRRm v HRR wild type, HRRwt) using the 15-gene panel HRRm was 0.42 (0.28-0.64) at all stages and 0.42 (0.27-0.65) at stages IIIC-IV. However, a prognostic difference was observed only between the BRCA mutation group and the HRRwt group, not between the non-BRCA HRRm group and the HRRwt group. For the subgroups of patients not using PARPis, the HR (95% CI) was 0.41 (0.24-0.68) at stages IIIC-IV.
CONCLUSIONS: This study provides evidence that 15-gene panel HRRm can predict the prognosis of EOC, of these only the BRCA1/2 mutations, not non-BRCA HRRm, contribute to prognosis prediction. Among patients without PARPis, the HRRm group presented a better PFS. This is the first study of this kind in the Chinese population.