title: Development of a deregulating microRNA panel for the detection of early relapse in postoperative colorectal cancer patients.
abstract: Colorectal cancer (CRC) is the third leading cause of cancer mortality worldwide and is associated with high recurrence and mortality, despite recent advancements in therapeutic strategies. MicroRNA (miR) deregulation is associated with CRC development and recurrence; therefore, miRs may be reliable biomarkers for detecting early relapse postoperatively.
  
  
  
  In this study ten candidates were identified using miR arrays: miR-7, miR-31, miR-93, miR-141, miR-195, miR-375, miR-429, miR-494, miR-650, and let-7b. Substantial differences were observed in their expression levels between early relapsed (recurrences within 12 months after surgery) and non-early relapsed CRC patients. The validation study, including 50 early relapsed and 54 non-early relapsed patients, confirmed miR expression alterations in cancer tissue samples.
  
  
  
  Using a miR real-time quantitative polymerase chain reaction (RT-qPCR), we observed that expression levels of miR-93, miR-195, and let-7b were significantly decreased, whereas those of miR-7, miR-141 and miR-494 showed increases that were more significant in the CRC tissue samples from the early relapsed patients than in those from the non-early relapsed patients. Disease-free survival and overall survival were significantly worse in the high miR-7, miR-141, and miR-494 expression subgroups and the low miR-93 and miR-195 expression subgroups (all P < 0.05). A panel of 6 miRs (miR-7, miR-93, miR-195, miR-141, miR-494, and let-7b), at a cut-off value of 2 deregulated miRs, distinguished early relapsed CRC from non-early relapsed CRC, with a sensitivity of 76.6 % and a specificity of 71.4 %. By combining this 6-miRs panel with 6 clinicopathologic factors, at a cut-off value of 4, distinguished early relapsed CRC from non-early relapsed CRC, with a sensitivity of 89.4 % and a specificity of 88.9 %.
  
  
  
  This study showed that the developed miR panel has the potential to improve predicting early relapse in CRC patients.
authors.affiliation: Department of Genomic Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Nursing, Shu-Zen College of Medicine and Management, Kaohsiung, Taiwan.
authors.forename: I-Ping
authors.initials: IP
authors.lastname: Yang
authors.affiliation: Division of General Surgery Medicine, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Division of Gastroenterology and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Hsiang-Lin
authors.initials: HL
authors.lastname: Tsai
authors.affiliation: Division of Gastroenterology and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.|Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100 Tzyou First Road, Kaohsiung, 807, Taiwan.
authors.forename: Zhi-Feng
authors.initials: ZF
authors.lastname: Miao
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Division of Gastroenterology and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.|Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100 Tzyou First Road, Kaohsiung, 807, Taiwan.
authors.forename: Ching-Wen
authors.initials: CW
authors.lastname: Huang
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chao-Hung
authors.initials: CH
authors.lastname: Kuo
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Jeng-Yih
authors.initials: JY
authors.lastname: Wu
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Wen-Ming
authors.initials: WM
authors.lastname: Wang
authors.affiliation: Department of Genomic Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Suh-Hang Hank
authors.initials: SH
authors.lastname: Juo
authors.affiliation: Department of Genomic Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. cy614112@ms14.hinet.net.|Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. cy614112@ms14.hinet.net.|Division of Gastroenterology and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. cy614112@ms14.hinet.net.|Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. cy614112@ms14.hinet.net.|Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100 Tzyou First Road, Kaohsiung, 807, Taiwan. cy614112@ms14.hinet.net.|Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan. cy614112@ms14.hinet.net.|Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. cy614112@ms14.hinet.net.|Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. cy614112@ms14.hinet.net.
authors.forename: Jaw-Yuan
authors.initials: JY
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery*; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D035683:MicroRNAs
keywords: Biomarker; Colorectal cancer; Early relapse; miR panel