title: MiR-139-5p as a novel serum biomarker for recurrence and metastasis in colorectal cancer.
abstract: Approximately 30-50% of colorectal cancer (CRC) patients who undergo curative resection subsequently experience tumor recurrence or metastasis. Although microRNAs (miRNAs) are a class of small noncoding RNAs frequently deregulated in various human malignancies, it remains unknown if these can help predict recurrence and metastasis in CRC patients. MiRNAs were initially screened using miRNA-microarray and miRNA-seq datasets with or without recurrence. Candidate miRNAs were then tested in two independent cohorts of 111 stage II/III and 139 stage I-III CRC patients, as well as serum samples and matched primary and metastatic liver tissues. An animal model of peritoneal dissemination was used to assess the oncogenic role of the target miRNA. Four candidate miRNAs were identified during the initial screening, and we subsequently validated upregulation of miR-139-5p in two independent clinical cohorts, wherein it associated with poor recurrence-free survival. Moreover, miR-139-5p were also upregulated in the serum of recurrence-positive CRC patients and yielded significantly shorter recurrence-free survival. Intriguingly, miR-139-5p was upregulated in metastatic liver tissues and negatively correlated with genes associated with epithelial-mesenchymal transition. Lastly, we showed that miR-139-5p overexpression enhanced peritoneal dissemination in a mouse model. In conclusion, we identified miR-139-5p as a novel biomarker for tumor recurrence and metastasis in CRC.
authors.affiliation: Center for Gastrointestinal Research, Center for Translational Genomics and Oncology, Baylor Scott &White Research Institute and Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas, USA.|Department of Gastroenterology and Oncology, Institutes of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Jinsei
authors.initials: J
authors.lastname: Miyoshi
authors.affiliation: Center for Gastrointestinal Research, Center for Translational Genomics and Oncology, Baylor Scott &White Research Institute and Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas, USA.
authors.forename: Shusuke
authors.initials: S
authors.lastname: Toden
authors.affiliation: Center for Gastrointestinal Research, Center for Translational Genomics and Oncology, Baylor Scott &White Research Institute and Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas, USA.|Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Graduate School of Medicine, Mie University, Mie, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Toiyama
authors.affiliation: Division of Medical Oncology, Mayo Clinic and Mayo Cancer Center, Rochester, Minnesota, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Alberts
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Graduate School of Medicine, Mie University, Mie, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Kusunoki
authors.affiliation: Division of Medical Oncology, Mayo Clinic and Mayo Cancer Center, Rochester, Minnesota, USA.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Sinicrope
authors.affiliation: Center for Gastrointestinal Research, Center for Translational Genomics and Oncology, Baylor Scott &White Research Institute and Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas, USA.
authors.forename: Ajay
authors.initials: A
authors.lastname: Goel
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; C555098:MIRN139 microRNA, human; D035683:MicroRNAs