Down-regulation of let-7a-5p predicts lymph node metastasis and prognosis in colorectal cancer: Implications for chemotherapy

Surg Oncol. 2016 Dec;25(4):429-434. doi: 10.1016/j.suronc.2016.05.016. Epub 2016 May 27.

Abstract

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.

Keywords: Colorectal cancer; HMGA2; Let-7a-5p; Metastasis; miR-21.

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / secondary*
  • Female
  • Follow-Up Studies
  • HMGA2 Protein / genetics
  • HMGA2 Protein / metabolism*
  • Humans
  • Immunoenzyme Techniques
  • Lymphatic Metastasis
  • Male
  • MicroRNAs / genetics*
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology*
  • Neoplasm Staging
  • Prognosis
  • Real-Time Polymerase Chain Reaction
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • HMGA2 Protein
  • MicroRNAs
  • mirnlet7 microRNA, human