Abstract

Recently, several microRNAs (miRNAs) have been reported as promising biomarkers for cancer detection and tumor recurrence risk. Due to its stability, miRNA can be accessed from samples stored in severe conditions, such as feces or formalin-fixed paraffin-embedded (FFPE) tissue. Fecal miRNA extracted from the residuum of fecal occult blood tests (FOBTs) was assessed to determine whether a combination of this fecal miRNA test (FmiRT) with FOBT could improve the false-negative rate of colorectal cancer (CRC) screening compared with FOBT alone. Expression of miR-106a in patients with both positive and negative FOBTs was significantly higher than in healthy volunteers. To identify a high-risk group for recurrence, miRNAs were extracted from FFPE samples of patients with stage II CRC. Tumor recurrence occurred at a significantly higher rate in patients with increased miR-181c expression than in those with lower expression. The recurrence rate in patients with stage II CRC with higher expression of miR-181c was similar to that of patients with stage III CRC who had been treated by surgical resection alone. As miRNAs are stable in several severe storage conditions, such as in fecal and FFPE samples, they could be valuable, accessible biomarkers for CRC, for use both in cancer screening and as predictors of recurrence.

Highlights

  • Colorectal cancer (CRC) is the second highest cause of cancer-related mortality worldwide [1]

  • Fecal miRNA extracted from the residuum of fecal occult blood tests (FOBTs) was assessed to determine whether a combination of this fecal miRNA test (FmiRT) with FOBT could improve the false-negative rate of colorectal cancer (CRC) screening compared with FOBT alone

  • In a multivariate analysis including pathological factors, increased expression of miR-181c was an independent predictive factor of recurrence [odds ratio (OR): 9.43, 95% confidence interval (CI): 2.57–34.48, P = 0.001], and an independent predictive factor of worse relapse-free survival (RFS) [hazard ratio (HR): 6.62, 95% CI: 2.08–21.28, P = 0.001]

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Summary

MicroRNA analysis of colorectal cancer using fecal and tissue samples

Division of Developmental Therapeutics, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, 277-8577, Japan. Several microRNAs (miRNAs) have been reported as promising biomarkers for cancer detection and tumor recurrence risk. MiRNA can be accessed from samples stored in severe conditions, such as feces or formalin-fixed paraffin-embedded (FFPE) tissue. Expression of miR-106a in patients with both positive and negative FOBTs was significantly higher than in healthy volunteers. To identify a high-risk group for recurrence, miRNAs were extracted from FFPE samples of patients with stage II CRC. Tumor recurrence occurred at a significantly higher rate in patients with increased miR-181c expression than in those with lower expression. As miRNAs are stable in several severe storage conditions, such as in fecal and FFPE samples, they could be valuable, accessible biomarkers for CRC, for use both in cancer screening and as predictors of recurrence.

Introduction
Fecal miRNA test to detect false negative FOBT results
Findings
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