The expression of BRCA1 and BRCA2 in epithelial ovarian cancer and their relationship with prognosis
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摘要: 目的 探讨乳腺癌易感基因1(BRCA1)、乳腺癌易感基因2(BRCA2)在上皮性卵巢癌(EOC)中的表达水平,并分析其与预后的关系。方法 选取2019年1月—2023年6月南通市肿瘤医院收治的98例EOC患者,采集术中切除的新鲜癌组织和癌旁组织,采用实时定量聚合酶链反应(qRT-PCR)检测组织中BRCA1、BRCA2 mRNA表达情况,分析其与临床病理特征的关系,并以Kaplan-Meier生存曲线和Cox回归模型分析其对EOC患者总生存期(OS)和无进展生存期(PFS)的影响。结果 EOC组织BRCA1、BRCA2 mRNA表达量、蛋白相对表达量均低于癌旁组织(P＜0.05)。腹腔积液量≥500 mL、国际妇产科学联合会(FIGO)分期Ⅲ—Ⅳ期、有淋巴结转移患者的BRCA1、BRCA2 mRNA表达低于无腹腔积液和腹腔积液量＜500 mL、FIGO分期Ⅰ—Ⅱ期及无淋巴结转移患者(P＜0.05)。中位随访时间27(9~50)个月,随访率95.92%(4例失访),随访期间39例(39.80%)复发,26例(26.53%)死亡。Kaplan-Meier生存分析显示,BRCA1、BRCA2 mRNA高表达者累积生存率高于低表达者(P＜0.05)。BRCA1、BRCA2 mRNA高表达者累积无进展生存率高于低表达者(P＜0.05)。多因素Cox回归分析显示化疗≤6疗程、腹腔积液量≥500 mL、FIGO分期Ⅲ+Ⅳ期及BRCA1、BRCA2 mRNA低表达是影响EOC患者OS的独立危险因素(P＜0.05)。术后残灶＞2 cm、化疗≤6疗程、腹腔积液量≥500 mL及BRCA1、BRCA2 mRNA低表达是影响EOC患者PFS的独立危险因素(P＜0.05)。结论 EOC癌变组织中BRCA1、BRCA2异常低表达,BRCA1、BRCA2 mRNA低表达与患者的临床病理特征关系密切,且影响患者PFS及OS。Abstract: Objective To investigate the expression of breast cancer susceptibility gene 1 (BRCA1) and BRCA2 in epithelial ovarian cancer (EOC), and analyze their relationship with prognosis.Methods A total of 98 EOC patients who were admitted to Nantong Cancer Hospital from January 2019 to June 2023 were selected. Their fresh cancer tissues and adjacent normal tissues intraoperatively resected were collected. The expression of BRCA1 and BRCA2 mRNA in the tissues were detected by real-time quantitative polymerase chain reaction (qRT-PCR). The relationship between the relative expression of BRCA1 and BRCA2 mRNA and clinicopathological features was analyzed, and their effect on overall survival (OS) and progression-free survival (PFS) of EOC patients were analyzed by Kaplan-Meier survival curves and Cox regression risk models.Results The BRCA1 and BRCA2 mRNA levels and relative protein expression in EOC tissues were lower than those in adjacent normal tissues (P<0.05). The levels of BRCA1 and BRCA2 mRNA in patients with ascites ≥500 mL, International Federation of Gynecology and Obstetrics (FIGO) stage Ⅲ—Ⅳ, and lymph node metastasis were lower than those in patients without ascites or with ascites <500 mL, with FIGO stage Ⅰ—Ⅱ, and without lymph node metastasis (P<0.05). The patients were followed up from 9 to 50 months, with a median follow-up time of 27 months, and a follow-up rate of 95.92% (4 patients were lost visited). During follow-up visits, 39 patients (39.80%) relapsed and 26 (26.53%) died. Kaplan-Meier survival analysis showed that the cumulative survival rate of patients with high expression of BRCA1 and BRCA2 mRNA was higher than that of those with low expression (P<0.05). Cumulative progression-free survival was higher in patients with high expression of BRCA1 and BRCA2 mRNA than in those with low expression (P<0.05). Multifactorial Cox regression analysis indicated that chemotherapy ≤6 courses, ascites ≥500 mL, FIGO stage Ⅲ+Ⅳ, and low expression of BRCA1 and BRCA2 mRNA were independent risk factors affecting OS in EOC patients (P<0.05). Postoperative residual foci >2 cm, chemotherapy≤6 courses, ascites ≥500 mL and low expression of BRCA1 and BRCA2 mRNA were independent risk factors affecting PFS in EOC patients (P<0.05).Conclusions Abnormally low expression of BRCA1 and BRCA2 in EOC tissues and low expression of BRCA1 and BRCA2 mRNA are closely related to the clinicopathologic features of patients and affected their PFS and OS.
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