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微小RNA-34b/c启动子区域多态性与中国汉族人群局部晚期食管鳞状细胞癌放化疗疗效的相关性

Association Between Polymorphisms in the Promoter Region of microRNA-34b/c and the Chemoradiotherapy Efficacy for Locally Advanced Esophageal Squamous Cell Carcinoma in Chinese Han Population.

作者信息

Bulibu Jilisihan, Wang Wei, Tang Yong, Li Na, Saifuding Keyoumu

机构信息

Department of Gastroenterology, The Affiliated Tumor Hospital of Xinjiang Medical University, No. 789, Suzhou East Street, Urumqi, 830000, the Xinjiang Uygur Autonomous Region, People's Republic of China.

出版信息

Pathol Oncol Res. 2019 Jan;25(1):421-427. doi: 10.1007/s12253-017-0366-4. Epub 2017 Dec 21.

Abstract

The study aims to explore the association between polymorphisms in the promoter region of microRNA-34b/c (miR-34b/c) and the chemoradiotherapy efficacy for locally advanced esophageal squamous cell carcinoma (ESCC) in Chinese Han population. A total of 175 locally advanced ESCC cases and 186 healthy individuals were enrolled as the case and control groups. Denaturing high performance liquid chromatography (DHPLC) was applied to determine the genotypes of subjects. Subjects in the case group were classified into complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). CR + PR were defined as the sensitive group, and SD + PD were defined as the resistance group. All patients were followed up for 3 ~ 36 months. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of rs4938723 in the promoter region of miR-34b/c in the chemoradiotherapy efficacy for patients with locally advanced ESCC. The distribution of genotype and allele of rs4938723 in the promoter region of miR-34b/c was significantly different between the case and control group (both P < 0.05), and CC genotype and C allele could decrease the risk of ESCC (CC genotype: OR = 0.57, 95%CI = 0.32 ~ 0.99, P = 0.045; C allele: OR = 0.72, 95%CI = 0.54 ~ 0.97, P = 0.032). MiR-34b/c rs4938723 was associated with ESCC TNM staging, differentiation degree, and lymph node metastasis (LNM) for ES CC patients (all P < 0.05). The chemoradiotherapy efficacy of patients with CC genotype was better than that of patients with (TT + TC) genotypes (P < 0.05). ROC curve results showed that the area under curve (AUC), sensitivity and specificity were 0.777, 85.1% and 71.3%, respectively. The average median progression free survival (PFS) of patients with (TT + TC) genotypes was significantly shorter than those patients with CC genotype (P < 0.05). Our study provides evidence that miR-34b/c rs4938723 is closely related with the chemoradiotherapy efficacy for locally advanced ESCC.

摘要

本研究旨在探讨微小RNA-34b/c(miR-34b/c)启动子区域多态性与中国汉族人群局部晚期食管鳞状细胞癌(ESCC)放化疗疗效之间的关联。共纳入175例局部晚期ESCC患者和186例健康个体作为病例组和对照组。采用变性高效液相色谱法(DHPLC)确定研究对象的基因型。病例组患者分为完全缓解(CR)、部分缓解(PR)、疾病稳定(SD)和疾病进展(PD)。CR+PR定义为敏感组,SD+PD定义为抵抗组。所有患者随访3至36个月。采用受试者工作特征(ROC)曲线评估miR-34b/c启动子区域rs4938723对局部晚期ESCC患者放化疗疗效的预测价值。miR-34b/c启动子区域rs4938723的基因型和等位基因分布在病例组和对照组之间存在显著差异(均P<0.05),CC基因型和C等位基因可降低ESCC风险(CC基因型:OR=0.57,95%CI=0.32至0.99,P=0.045;C等位基因:OR=0.72,95%CI=0.54至0.97,P=0.032)。miR-34b/c rs4938723与ESCC患者的TNM分期、分化程度及淋巴结转移(LNM)相关(均P<0.05)。CC基因型患者的放化疗疗效优于(TT+TC)基因型患者(P<0.05)。ROC曲线结果显示,曲线下面积(AUC)、敏感度和特异度分别为0.777、85.1%和71.3%。(TT+TC)基因型患者的平均无进展生存期(PFS)显著短于CC基因型患者(P<0.05)。我们的研究提供了证据表明miR-34b/c rs4938723与局部晚期ESCC的放化疗疗效密切相关。

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