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BRCA1 mRNA 表达作为预测和预后标志物在接受顺铂或多西紫杉醇为基础的化疗/放化疗治疗的晚期食管鳞状细胞癌中的应用。

BRCA1 mRNA expression as a predictive and prognostic marker in advanced esophageal squamous cell carcinoma treated with cisplatin- or docetaxel-based chemotherapy/chemoradiotherapy.

机构信息

Department of Medical Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, China.

出版信息

PLoS One. 2013;8(1):e52589. doi: 10.1371/journal.pone.0052589. Epub 2013 Jan 9.

Abstract

BACKGROUND

The molecular backgrounds that determine therapeutic effectiveness in esophageal cancer remain largely unknown. Breast cancer susceptibility gene 1 (BRCA1) expression has been found to switch the response to cisplatin- or paclitaxel-based chemotherapy. It remains unclear how variations in BRCA1 expression influence clinical outcomes in esophageal cancer.

PATIENTS AND METHODS

Quantitative real-time polymerase chain reaction (qPCR) was performed to examine BRCA1 mRNA expressions in paraffin-embedded specimens from 144 patients with advanced or metastatic esophageal squamous cell carcinoma who received cisplatin- or docetaxel-based first-line treatments.

RESULTS

Low BRCA1 mRNA expression correlated with increased response rate (RR; P = 0.025 and 0.017, respectively) and median overall survival (mOS; P = 0.002 and P<0.001, respectively) in cisplatin-based chemotherapy or chemoradiotherapy group and also correlated with decreased RR (P = 0.017 and 0.024, respectively) and mOS (both P<0.001) in docetaxel-based chemotherapy or chemoradiotherapy group. Multivariate analysis revealed that low BRCA1 expression was an independent prognostic factor in cisplatin-based chemotherapy (HR 0.29; 95%CI 0.12-0.71; P = 0.007) or chemoradiotherapy (HR 0.12; 95%CI 0.04-0.37; P<0.001) group and higher risk for mortality in docetaxel-based chemotherapy (HR 5.02; 95%CI 2.05-12.28; P<0.001) or chemoradiotherapy (HR 7.02; 95%CI 2.37-27.77; P<0.001) group.

CONCLUSIONS

BRCA1 mRNA expression could be used as a predictive and prognostic marker in esophageal cancer who underwent first-line cisplatin- or docetaxel-based treatments.

摘要

背景

食管癌治疗效果的分子背景在很大程度上仍不清楚。乳腺癌易感基因 1(BRCA1)的表达已被发现可改变顺铂或紫杉醇为基础的化疗反应。BRCA1 表达的变化如何影响食管癌的临床结局尚不清楚。

患者和方法

采用定量实时聚合酶链反应(qPCR)检测 144 例接受顺铂或多西紫杉醇为基础的一线治疗的晚期或转移性食管鳞状细胞癌患者石蜡包埋标本中 BRCA1 mRNA 的表达。

结果

低 BRCA1 mRNA 表达与顺铂为基础化疗或放化疗组的应答率(RR;P=0.025 和 0.017)和中位总生存期(mOS;P=0.002 和 P<0.001)增加相关,也与 RR 降低(P=0.017 和 0.024)和 mOS 降低(均 P<0.001)相关在多西紫杉醇为基础的化疗或放化疗组中。多变量分析显示,低 BRCA1 表达是顺铂为基础化疗(HR 0.29;95%CI 0.12-0.71;P=0.007)或放化疗(HR 0.12;95%CI 0.04-0.37;P<0.001)组的独立预后因素,并且在多西紫杉醇为基础的化疗(HR 5.02;95%CI 2.05-12.28;P<0.001)或放化疗(HR 7.02;95%CI 2.37-27.77;P<0.001)组的死亡率更高。

结论

BRCA1 mRNA 表达可作为接受顺铂或多西紫杉醇为基础一线治疗的食管癌患者的预测和预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/262e/3541365/088dcd077fb7/pone.0052589.g001.jpg

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