Correlation analysis of BRCA1/2 gene status and clinicopathological features in patients with epithelial ovarian cancer
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摘要:
目的 探讨上皮性卵巢癌患者的BRCA1/2胚系突变状态与其临床病理特征的关系，从而为患者制定出精准个体化治疗方案。 方法 选择2019年12月1日—2021年10月31日就诊于蚌埠医学院第一附属医院妇瘤科并具有乳腺癌易感基因(breast cancer susceptibility gene，BRCA1/2)胚系突变检测结果的上皮性卵巢癌患者为研究对象，根据BRCA1/2基因状态分为突变组及野生组，对2组患者的临床病理特征数据进行统计分析。 结果 2组患者相比，突变组患者初始CA125水平(P=0.016)和FIGO分期(P=0.010)明显高于野生组，有家族史者在突变组中所占比例更高(P=0.026)，并且腹水阳性者在突变组患者中更多(P=0.020)，无铂间期也更长(P=0.044)，差异均有统计学意义(均P＜0.05)。晚期患者的初始治疗方式、减瘤满意程度、复发情况、一线铂类药物化疗敏感性、年龄差异均无统计学意义(均P＞0.05)。 结论 在上皮性卵巢癌患者中，BRCA1/2基因突变患者的无铂间期更长，有卵巢癌家族史、FIGO分期较高、肿瘤标记物水平高、腹水阳性的病例胚系BRCA1/2基因突变阳性的可能性更大，对此类患者尽早进行基因检测，及时给予PARP抑制剂等积极干预可能会为患者谋求更长生存时间。 Abstract:Objective This study was performed to investigate the relationship between BRCA1/2 germ line mutation status and clinicopathological characteristics in epithelial ovarian cancer patients, so as to develop precise individualized treatment plan for patients. Methods Patients with epithelial ovarian cancer who visited the Department of Gynecologic Oncology in the First Affiliated Hospital of Bengbu Medical College from December 1, 2019 to October 31, 2021 and had germline mutation test results of breast cancer susceptibility gene (BRCA1/2) were selected for the study. According to the results of gene detection, they were divided into gBRCA1/2m (+) group (mutation group) and gBRCA1/2m (-) group (wild-type group). The clinicopathological characteristics of the two groups of patients were statistically analyzed. Results Compared between the two groups of patients, the initial CA125 level (P=0.016) and FIGO stage (P=0.010) of patients in the mutation group were significantly higher than those in the wild-type group, the proportion of family history was higher (P=0.026) in the mutation group, and the patients with positive ascites were more common (P=0.020) in the mutation group. The platinum interval was also longer (P=0.044) and the differences were statistically significant (all P < 0.05). There were no significant differences in the initial treatment method, satisfaction with tumour cytoreduction, recurrence, sensitivity to first-line platinum-based chemotherapy and age in advanced patients (all P>0.05). Conclusion Among patients with epithelial ovarian cancer, patients with BRCA1/2 gene mutations have a longer platinum-free interval, and those with a family history of ovarian cancer, higher FIGO stage, high tumor marker levels and positive ascites are more likely to have a positive germline BRCA1/2 mutation. Early genetic testing and timely aggressive intervention such as PARP inhibitors in these patients may result in a longer survival time for the patient. -
Key words:
- BRCA1/2 gene /
- Ovarian cancer /
- Germline mutation /
- PARP inhibitor
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表 1 BRCA1/2基因突变组及野生组临床病理特征比较[例(%)]
Table 1. Comparison of clinicopathological features of BRCA1/2 gene mutant group and wild group[cases (%)]
项目 BRCA1/2突变组(n=29) BRCA1/2野生组(n=67) χ2值 P值 年龄 0.122 0.727 ≥45岁 25(86.2) 61(91.0) ＜45岁 4(13.8) 6(9.0) 家族史 0.026b 有 3(10.3) 0 无 26(89.7) 67(100.0) 分化程度 1.225 0.268 中高级别 28(96.6) 58(86.6) 低级别 1(3.4) 9(13.4) 病理类型 0.031b 浆液性 29(100.0) 56(83.6) 非浆液性a 0 11(16.4) FIGO分期 6.639 0.010 Ⅰ~Ⅱ期 2(6.9) 21(31.3) Ⅲ~Ⅳ期 27(93.1) 46(68.7) 腹水 5.407 0.020 阳性 24(82.8) 39(58.2) 阴性 5(17.2) 28(41.8) 腹腔热灌注 1.662 0.197 有 14(48.3) 23(34.3) 无 15(51.7) 44(65.7) 肠切除 2.074 0.150 有 5(17.2) 5(7.5) 无 24(82.8) 62(92.5) 化疗次数 2.723 0.099 6次 7(24.1) 28(41.8) ＞6次 22(75.9) 39(58.2) 减瘤满意度 0.082 0.774 满意(R0/R1) 28(96.6) 62(92.5) 不满意(R2) 1(3.4) 5(7.5) 注：a为非浆液性癌，包括黏液性癌、浆黏液性癌、子宫内膜样癌等其他病理类型。b为采用Fisher精确检验。 
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表 2 晚期突变组及野生组患者初始治疗方式比较[例(%)]
Table 2. Comparison of initial treatment methods of patients with advanced mutation group and wild group[cases (%)]
组别 例数 初始治疗方式 PDS IDS 突变组 27 13(48.1) 14(51.9) 野生组 46 15(32.6) 31(67.4) 注：2组初始治疗方式比较，χ2=1.738，P=0.187。
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表 3 复发突变组及野生组患者铂反应性比较[例(%)]
Table 3. Comparison of platinum reactivity in patients with recurrent mutation group and wild group[cases (%)]
组别 例数 铂类药物反应性 铂敏感 铂耐药 突变组 9 7(77.8) 2(22.2) 野生组 22 12(54.5) 10(45.5) 注：2组铂类反应性比较，χ2=0.639，P=0.418。
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