Liu Tsang-Pai, Huang Chi-Chou, Yeh Ken-Tu, Ke Tao-Wei, Wei Po-Li, Yang Ji-Rui, Cheng Ya-Wen
Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei, Taiwan; Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; Division of Colorectal Surgery, Department of Surgery, MacKay Memorial Hospital, Taipei, Taiwan.
School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Division of General Surgery, Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan.
Surg Oncol. 2016 Dec;25(4):429-434. doi: 10.1016/j.suronc.2016.05.016. Epub 2016 May 27.
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. Kaplan-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.
结直肠癌(CRC)指南建议根据淋巴结转移水平进行辅助化疗。Let-7a-5p是一种微小RNA,它通过靶向HMGA2抑制迁移、侵袭以及上皮-间质转化。本研究的目的是探讨Let-7a-5p在CRC临床影响中的作用。在本研究中,纳入了192例CRC患者。通过实时PCR和免疫组织化学分析血清和肿瘤组织中Let-7a-5p和HMGA2的表达。采用Kaplan-Meier分析来分析主要结局,包括生存率和肿瘤复发情况。CRC患者肿瘤组织中Let-7a-5p的表达与肿瘤大小、分期和淋巴结转移显著负相关(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蛋白之间存在负相关(p < 0.0001)。Let-7a-5p低/HMGA2高的患者的总生存期(OS)和无病生存期(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的表达水平与肿瘤组织中的Let-7a-5p呈正相关。血清中Let-7a-5p的表达水平也可作为预测临床结局的生物标志物。我们建议,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。这些结果可能对化疗建议有启示意义。