miR-181b 和 miR-21 在接受 S-1/奥沙利铂或多柔比星/奥沙利铂治疗的胃癌患者中的预后意义。
Prognostic significance of miR-181b and miR-21 in gastric cancer patients treated with S-1/Oxaliplatin or Doxifluridine/Oxaliplatin.
机构信息
Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, People's Republic of China.
出版信息
PLoS One. 2011;6(8):e23271. doi: 10.1371/journal.pone.0023271. Epub 2011 Aug 18.
BACKGROUND
The goal of this study is to evaluate the effectiveness of S-1/Oxaliplatin vs. Doxifluridine/Oxaliplatin regimen and to identify miRNAs as potential prognostic biomarkers in gastric cancer patients. The expression of candidate miRNAs was quantified from fifty-five late stage gastric cancer FFPE specimens.
EXPERIMENTAL DESIGN
Gastric cancer patients with KPS>70 were recruited for the trial. The control group was treated with 400 mg/twice/day Doxifluridine plus i.v. with Oxaliplatin at 130 mg/m(2)/first day/4 week cycle. The testing group was treated with S-1 at 40 mg/twice/day/4 week cycle plus i.v. with Oxaliplatin at 130 mg/m(2)/first day/4 week cycle. Total RNAs were extracted from normal and gastric tumor specimens. The levels of miRNAs were quantified using real time qRT-PCR expression analysis.
RESULTS
The overall objective response rate (CR+PR) of patients treated with S-1/Oxaliplatin was 33.3% (CR+PR) vs. 17.6% (CR+PR) with Doxifluridine/Oxaliplatin for advanced stage gastric cancer patients. The average overall survival for patients treated with S-1/Oxaliplatin was 7.80 month vs. 7.30 month with patients treated with Doxifluridine/Oxaliplatin. The expression of miR-181b (P = 0.022) and miR-21 (P = 0.0029) was significantly overexpressed in gastric tumors compared to normal gastric tissues. Kaplan-Meier survival analysis revealed that low levels of miR-21 expression (Log rank test, hazard ratio: 0.17, CI = 0.06-0.45; P = 0.0004) and miR-181b (Log rank test, hazard ratio: 0.37, CI = 0.16-0.87; P = 0.018) are closely associated with better patient's overall survival for both S-1 and Doxifluridine based regimens.
CONCLUSION
Patients treated with S-1/Oxaliplatin had a better response than those treated with Doxifluridine/Oxaliplatin. miR-21 and miR-181b hold great potential as prognostic biomarkers in late stage gastric cancer.
背景
本研究旨在评估 S-1/奥沙利铂与多柔比星/奥沙利铂方案的有效性，并确定 miRNA 作为晚期胃癌患者的潜在预后生物标志物。从 55 例晚期胃癌 FFPE 标本中定量检测候选 miRNA 的表达。
实验设计
招募 KPS>70 的胃癌患者进行试验。对照组给予 400mg/次/日多柔比星+静脉注射奥沙利铂 130mg/m2/第 1 天/4 周周期。实验组给予 S-1 40mg/次/日/4 周周期+静脉注射奥沙利铂 130mg/m2/第 1 天/4 周周期。从正常和胃癌组织标本中提取总 RNA。采用实时 qRT-PCR 表达分析定量检测 miRNA 水平。
结果
S-1/奥沙利铂治疗晚期胃癌患者的总客观缓解率（CR+PR）为 33.3%（CR+PR），而多柔比星/奥沙利铂治疗组为 17.6%（CR+PR）。S-1/奥沙利铂治疗组患者的平均总生存期为 7.80 个月，而多柔比星/奥沙利铂治疗组为 7.30 个月。与正常胃组织相比，miR-181b（P=0.022）和 miR-21（P=0.0029）在胃癌组织中表达明显上调。Kaplan-Meier 生存分析显示，低水平 miR-21 表达（Log rank 检验，危险比：0.17，CI=0.06-0.45；P=0.0004）和 miR-181b（Log rank 检验，危险比：0.37，CI=0.16-0.87；P=0.018）与 S-1 和多柔比星为基础的方案患者的总生存期密切相关。
结论
S-1/奥沙利铂治疗组患者的反应优于多柔比星/奥沙利铂治疗组。miR-21 和 miR-181b 作为晚期胃癌患者的预后生物标志物具有很大的潜力。
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