MiR-139-5p as a novel serum biomarker for recurrence and metastasis in colorectal cancer

Jinsei Miyoshi, Shusuke Toden, Kazuhiro Yoshida, Yuji Toiyama, Steven Robert Alberts, Masato Kusunoki, Frank A Sinicrope, Ajay Goel

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Article number43393
JournalScientific Reports
Volume7
DOIs
StatePublished - Mar 6 2017

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MicroRNAs
Colorectal Neoplasms
Biomarkers
Neoplasm Metastasis
Recurrence
Serum
Small Untranslated RNA
Epithelial-Mesenchymal Transition
Survival
Liver
Tumor Biomarkers
Neoplasms
Up-Regulation
Animal Models
Genes

ASJC Scopus subject areas

  • General

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MiR-139-5p as a novel serum biomarker for recurrence and metastasis in colorectal cancer. / Miyoshi, Jinsei; Toden, Shusuke; Yoshida, Kazuhiro; Toiyama, Yuji; Alberts, Steven Robert; Kusunoki, Masato; Sinicrope, Frank A; Goel, Ajay.

In: Scientific Reports, Vol. 7, 43393, 06.03.2017.

Research output: Contribution to journalArticle

Miyoshi, Jinsei ; Toden, Shusuke ; Yoshida, Kazuhiro ; Toiyama, Yuji ; Alberts, Steven Robert ; Kusunoki, Masato ; Sinicrope, Frank A ; Goel, Ajay. / MiR-139-5p as a novel serum biomarker for recurrence and metastasis in colorectal cancer. In: Scientific Reports. 2017 ; Vol. 7.
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