Down-regulation of let-7a-5p predicts lymph node metastasis and prognosis in colorectal cancer: Implications for chemotherapy
Down-regulation of let-7a-5p predicts lymph node metastasis and prognosis in colorectal cancer: Implications for chemotherapy
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DOI：
10.1016/j.suronc.2016.05.016
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发表时间：
2016-12-01
影响因子：
2.3
通讯作者：
Cheng, Ya-Wen
中科院分区：
文献类型：
--
作者：
Liu, Tsang-Pai;Huang, Chi-Chou;Cheng, Ya-Wen
结直肠癌（CRC）指南根据淋巴结转移程度推荐辅助化疗。 Let-7a-5p是一种microRNA，通过靶向HMGA2来抑制迁移、侵袭以及上皮间质转化。本研究的目的是调查 let 7a-5p 在 CRC 临床影响中的作用。在这项研究中，招募了 192 名 CRC 患者。采用实时荧光定量PCR和免疫组化方法分析血清和肿瘤组织中let-7a-5p和HMGA2的表达。 Kaplane-Meier 分析用于分析主要结局，包括生存率和肿瘤复发。 CRC患者肿瘤组织中let-7a-5p的表达与肿瘤大小、分期和淋巴结转移呈显着负相关（肿瘤大小p=0.024，分期p<0.0001，淋巴结转移p<0.0001）。 let-7a-5p 水平与 HMGA2 蛋白水平呈负相关 (p < 0.0001)。 let-7a-5p低/HMGA2高患者的总生存（OS）和无病生存（DFS）率低于let-7a-5p高/HMGA2高、let-7a-5p高/HMGA2低和let-7a-5p低/HMGA2低的患者。此外，CRC患者血清中let-7a-5p的表达水平与CRC患者肿瘤组织中let-7a-5p的表达水平呈正相关。血清中let-7a-5p的表达水平也可以用作预测临床结果的生物标志物。我们认为CRC患者血清和肿瘤组织中let-7a-5p的下调可用于预测淋巴结转移和疾病预后。这些结果可能与化疗建议有关。 (C) 2016 Elsevier Ltd. 保留所有权利。
Colorectal cancer (CRC) guidelines recommend adjuvant chemotherapy according to the level of lymph node metastasis. Let-7a-5p is a microRNA, which inhibits migration, invasion, as well as the epithelial-mesenchymal transition by targeting HMGA2. The aim of this study was to investigate the role of let 7a-5p in the clinical impact of CRC. In this study, one hundred and ninety-two CRC patients were enrolled. The expression of let-7a-5p and HMGA2 in serum and tumour tissues were analysed by real-time PCR and immunohistochemistry. Kaplane-Meier analysis was used to analyse primary outcomes, including the survival and tumour recurrence. The expression of let-7a-5p in tumour tissues was significantly negative correlated with the tumour size, stage and lymph node metastasis in CRC patients (p = 0.024 for tumour size, p < 0.0001 for stage and p < 0.0001 for lymph node metastasis). There was a negative correlation between the levels of let-7a-5p and the HMGA2 protein (p < 0.0001). The overall survival (OS) and disease-free survival (DFS) rates of patients with let-7a-5p low/HMGA2 high were poorer than those with let-7a-5p high/HMGA2 high, let-7a-5p high/HMGA2 low and let-7a-5p low/HMGA2 low. In addition, the expression levels of let-7a-5p in serums were positively correlated with let 7a-5p in the tumour tissues of the CRC patients. The expression levels of let-7a-5p in serums also could be used as a biomarker to predict clinical outcome. We suggest that down-regulation of let-7a-5p in serums and tumour tissues of CRC patients could be used to predict lymph node metastasis and the disease prognosis. These results could be implicated for chemotherapy suggestion. (C) 2016 Elsevier Ltd. All rights reserved.