摘要
目的:初步探讨卵巢癌患者胚系BRCA1/2基因突变状态,分析其与临床病理特征的关系及对生存预后的影响。方法:对2015年1月至2020年1月在南京医科大学第一附属医院妇科诊断为上皮性卵巢癌的82例患者进行BRCA1/2基因序列突变检测,分析患者BRCA1/2基因致病性突变情况,探讨其与临床病理特征包括发病年龄、月经状态、FIGO分期、组织学分级、病理类型、铂敏感性、CA125水平、淋巴结转移、大网膜饼、膈顶转移、结肠侵犯等的相关性。单因素及多因素COX回归分析研究各因素对生存预后的影响。结果:82例上皮性卵巢癌患者中,BRCA1胚系致病性突变率为20.73%,BRCA2胚系致病性突变率为9.75%,总突变率为30.48%。共发现18个致病突变位点及2个意义未明的突变位点。单因素分析发现BRCA1/2基因突变与病理类型、铂敏感、新辅助化疗相关,具有统计学意义(P<0.05);另外,BRCA1/2突变组与BRCA1/2野生组相比,中位无进展生存期(progression free survival,PFS)分别为18.6个月和12.8个月,突变组较未突变组中位PFS延长了5.8个月(P<0.05)。多因素COX回归分析显示,铂敏感(P<0.001;HR=0.023;95%CI:0.008~0.072)和是否存在结直肠侵犯(P=0.005;HR=2.810;95%CI:1.387~5.693)为卵巢癌PFS的独立预后因素。结论:上皮性卵巢癌患者中具有较高的BRCA1/2基因突变率,且与恶性程度较高的浆液性癌病理类型有关;BRCA1/2基因突变的患者多对铂敏感,预后较好。然而,BRCA突变状态并非是上皮性卵巢癌PFS的独立预后因素,还需更大规模的前瞻性对照临床研究对其对生存预后的影响进行探索。对突变位点的检测将有助于评估疾病风险和预测患者病情进展,具有一定的临床意义。
Objective:To explore the status of BRCA1/2 mutation in ovarian cancer patients,analyze its relationship to clinicopathological characteristics,and its influences on survival of ovarian cancer patients.Methods:BRCA1/2 mutation was detected in 82 patients diagnosed as epithelial ov arian cancer in the First Affiliated Hospital of Nanjing Medical University from January 2015 to January 2020.The pathogenic mutation of BRCA1/2 in patients was analyzed,and its relationship to clinicopathological characteristics of patients such as age,menstrual state,FIGO stage,histological grade,pathological type,platinum sensitivity,CA125 level,lymph node metastasis,greater omentum metastasis,diaphragmatic metastasis,colon invasion were further discussed.Univariate and multivariate COX regression analyses were used to investigate the factors affecting progression-free survival(PFS).Results:Among the 82 patients with epithelial ovarian cancer,the pathogenic mutation rates of BRCA1 and BRCA2 were 20.73%and 9.75%respectively,with the total rate of 30.48%.18 pathogenic mutation sites and 2 mutations with unknown significance were found.Univariate Cox analysis showed that BRCA1/2 gene mutation was associated with pathologic type,platinum sensitivity and neoadjuvant chemotherapy(P<0.05).The median PFS in the BRCA1/2 mutant-type group was longer(5.8 months)than that in the BRCA1/2 wild-type group(P<0.05).Multivariate Cox regression analysis showed that platinum sensitivity(HR=0.023,95%CI:O.008-0.072,P<0.0001)and colorectal invasion(HR=2.810,95%CI:1.387-5.693,P=0.005)were independent prognostic factors for PFS of ovarian cancer patients.Conclusion:There is a high frequency of BRCA1/2 mutation in epithelial ovarian cancer patients,and it is related to the pathological type of serous carcinoma with higher malignancy.Most of the patients with BRCA1/2 mutation are platinum sensitive,and have a good prognosis.BRCA1/2 mutation status,however,is not an independent prognostic factor of PFS,highlighting more large-scale clinical controlled prospective studies.The detection of BRCA1/2 mutation will help to predict and assess the risk and progression of diseases,which has certain clinical significance.
作者
孙国栋
孟黄洋
姜旖
袁琳
周树林
程文俊
Sun Guodong;Meng Huangyang;Jiang Yi;Yuan Lin;Zhou Shulin;Cheng Wenjun(Department of Gynecology,the First Afilited Hospital of Nanjing Medical University,Nanjing 210029,Jiangsu,China)
出处
《肿瘤预防与治疗》
2021年第11期1005-1012,共8页
Journal of Cancer Control And Treatment
基金
国家自然科学基金(编号:81872119)
江苏省青年医学重点人才(编号:QNRC2016610)
江苏省妇幼保健协会科研项目(编号:FYX201909)
江苏省医学创新团队(编号:CXTDA2017008)。
关键词
BRCA突变
卵巢癌
突变分析
临床病理
PFS
BRCA1/2 mutation
Ovarian cancer
Mutation analysis
Clinicopathological characteristics
Progression-free survival
