RRM1、BRCA1表达与ⅢB/Ⅳ期肺鳞癌患者GP方案化疗疗效的相关性研究
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The correlation of chemotherapeutic efficacy with ribonucleotide reductase subunit l and breast cancer susceptibility gene 1 protein expression in the stage ⅢB/Ⅳ squaomas lung cancer patients
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    摘要:

    目的:观察肿瘤组织核糖核酸调节亚单位1(RRM1)-乳腺癌易感基因1(BRCA1)表达与ⅢB/Ⅳ期肺鳞癌采用吉西他滨联合顺铂(GP)方案化疗疗效的相关性。方法:初治ⅢB/Ⅳ期肺鳞癌且体能状态(PS)评分0~2分-预计生存期≥3个月的患者入选本研究。入选患者均进行GP方案化疗,每3周为1个周期,每2个周期评价1次疗效,共4个周期,无效者更换二线化疗方案。免疫组化检测肿瘤组织中RRM1-BRCA1表达。根据RRM1-BRCA1表达高低分为A组(RRM1-/BRCA1-)-B组(RRM1+/BRCA1+)-C组(RRM1+/BRCA1-)-D组(RRM1-/BRCA1+)。评价疗效指标:客观反应率(RR)-总生存时间(OS)-肿瘤至进展时间(TTP)。结果:①入组78例ⅢB/Ⅳ期肺鳞癌患者,RRM1-BRCA1表达阳性率分别为47.4%(37/78)-51.3%(40/78),RRM1-BRCA1不同表达的患者临床特征比较差异无统计学意义; ②78例患者A组22例,B组21例,C组19例,D组16例。化疗前4组间的临床特征比较差异无统计学意义。4组患者RR分别为59.1%-38.1%-42.1%-43.8%;OS分别为(617.4 ± 19.6)-(299.2 ± 20.5)-(336.6 ± 22.7)-(324.7 ± 24.2)d;TTP分别为(274.9 ± 21.8)-(138.8 ± 18.0)-(172.3 ± 17.3)-(167.3 ± 19.8)d。其中A组的RR-OS及TTP均优于其他3组,差异有统计学意义(P值分别为0.039-0.000和0.000)。结论:RRM1-BRCA1可作为GP方案疗效的预测分子;RRM1-BRCA1低表达的肺鳞癌患者,可能是GP化疗方案的优势人群。

    Abstract:

    Objective:To determine whether the protein expression of ribonucleotide reductase subunit 1(RRM1) and breast cancer susceptibility gene 1(BRCA1) in tumor tissue could predict the efficacy of gemcitabine combined with cisplatin (GP) on stage ⅢB/Ⅳsquaomas lung cancer. Methods:A total of 89 stage ⅢB/Ⅳsquaomas lung cancer patients were included,only 78 patients were evaluated. Bronchoscopy or lung puncture tumor biopsies samples were obtained and RRM1,BRCA1 protein expression were examined immunohistochemically before chemotherapy,then the patients were randomly assigned to received 4 cycles of GP chemotherapy regiments. Follow-up was done afterwards until the patient died or could not be informed. Response rate (RR),overall survival (OS) and time to tumor progression (TTP) were assessed. Results:Among 78 evaluated patients,the positive expression rates of RRM1 and BRCA1 were 47.4%(37/78) and 51.3%(40/78),respectively. There was no significant difference between positive expression rates and patients’ clinical characteristics. According to the different levels of RRM1 and BRCA1,the patients were divided into four groups:group A (low expression of both RRM1 and BRCA1),group B (high expression of both RRM1 and BRCA1),group C (high expression of only RRM1) and group D (high expression of only BRCA1). The RR was higher in group A than in other three groups (group A 59.1%,group B 38.1%,group C 42.1 %,group D 43.8%). The OS and TTP were longer in group A than in other three groups[OS:group A(617.4 ± 19.6)days,group B(299.2 ± 20.5)days,group C (336.6 ± 22.7)days,group D(324.7 ± 24.2)days;TTP:group A(274.9 ± 21.8)days,group B(138.8 ± 18.0)days, group C(172.5 ± 17.3)days, group D(167.6 ± 19.8)days]. There were no significant difference among group B,C,and D. Conclusion:The expression level of RRM1 and BRCA1 in sequomas lung cancer is probably predictive factor of the efficacy of GP chemotherapy regiments. It is more suitable for squaomas lung cancer patients who expressing lower RRM1 and BRCA1 to adopt GP chemotherapy regiments.

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万一元,程劲松,惠红霞,王晓炜,吴 健. RRM1、BRCA1表达与ⅢB/Ⅳ期肺鳞癌患者GP方案化疗疗效的相关性研究[J].南京医科大学学报(自然科学版),2013,(10):1405-1409

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  • 收稿日期:2013-07-09
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  • 在线发布日期: 2013-10-23
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