Down-regulation of let-7a-5p predicts lymph node metastasis and prognosis in colorectal cancer: Implications for chemotherapy.
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.
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.
Tsang-Pai
TP
Liu
School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Division of General Surgery, Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan.
Chi-Chou
CC
Huang
Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan.
Ken-Tu
KT
Yeh
Division of General Surgery, Department of Surgery, China Medical University Hospital, Taichung, Taiwan.
Tao-Wei
TW
Ke
Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; Division of General Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei, Taiwan; Cancer Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
Po-Li
PL
Wei
Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
Ji-Rui
JR
Yang
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; Cancer Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan. Electronic address: ywc@tmu.edu.tw.
Ya-Wen
YW
Cheng
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000556:secondary*; D005260:Female; D005500:Follow-Up Studies; D025743:HMGA2 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D015996:Survival Rate
D014408:Biomarkers, Tumor; D025743:HMGA2 Protein; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human
Colorectal cancer; HMGA2; Let-7a-5p; Metastasis; miR-21