Yi Huan, Li Linhong, Huang Jimiao, Ma Zhiming, Li Hongping, Chen Jian, Zheng Xiangqin, Chen Jingjing, He Haixin, Song Jianrong
Department of Gynecology Oncology, Fujian Key Laboratory of Women and Children's Critical Diseases Research [Fujian Maternity and Child Health Hospital(Fujian Women and Children's Hospital)], Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics and Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China.
Research and Development Division, Oriomics Biotech Inc, Hangzhou, China.
Front Mol Biosci. 2022 Jun 13;9:906922. doi: 10.3389/fmolb.2022.906922. eCollection 2022.
Identifying BRCA mutations and homologous recombination deficiency (HRD) is the key to choosing patients for poly (ADP-ribose) polymerase inhibitor (PARPi) therapy. At present, a large amount of research focuses on the application of HRD detection in ovarian cancer. However, few studies have discussed the relationship between HRD detection and postoperative survival in patients with epithelial ovarian cancer (EOC). This study included 38 consecutive patients with EOC who underwent cytoreduction surgery. Owing to tissue availability, only 29 patients underwent molecular profiling and survival analysis. Overall, 21 (72.4%) tumors had HRD scores of ≥42. Mutations in BRCA were observed in 5/29 (17.2%) patients. In this cohort, an HRD score of ≥42 was more common in serous ovarian tumors. We found no statistically significant association between homologous recombination repair (HRR) genes and HRD scores except for tumor protein P53 (TP53) mutation. We also found a strong positive association between HRD scores and chromosomal instability (CIN). In the survival analysis, an HRD score of >23 was correlated with better postoperative progression-free survival (pPFS). With increased depth of research, an appropriate HRD score threshold may serve as a prognostic tool and should be assessed in future studies to predict the clinical value of PARPi.
识别BRCA突变和同源重组缺陷(HRD)是选择聚(ADP - 核糖)聚合酶抑制剂(PARPi)治疗患者的关键。目前,大量研究集中在HRD检测在卵巢癌中的应用。然而,很少有研究讨论HRD检测与上皮性卵巢癌(EOC)患者术后生存之间的关系。本研究纳入了38例连续接受肿瘤细胞减灭术的EOC患者。由于组织可用性,只有29例患者进行了分子分析和生存分析。总体而言,21例(72.4%)肿瘤的HRD评分≥42。29例患者中有5例(17.2%)观察到BRCA突变。在该队列中,HRD评分≥42在浆液性卵巢肿瘤中更为常见。除肿瘤蛋白P53(TP53)突变外,我们发现同源重组修复(HRR)基因与HRD评分之间无统计学显著关联。我们还发现HRD评分与染色体不稳定性(CIN)之间存在强正相关。在生存分析中,HRD评分>23与更好的术后无进展生存期(pPFS)相关。随着研究深度的增加,合适的HRD评分阈值可能作为一种预后工具,未来研究应评估其预测PARPi临床价值的能力。