Abstract

Simple SummaryEarly diagnosis is critically important to achieve life-saving therapy for colorectal cancer (CRC). Since colonoscopy is not suitable as a screening method for CRC due to its invasiveness and high-cost, reliable and non-invasive diagnostic biomarkers are hopeful for CRC. In this case-control study, we established completely non-invasive, novel urinary microRNA (miRNA) biomarker panel combining miR-129-1-3p and miR-566 for the diagnosis of CRC. In the independent age- and sex-matched three cohorts comprising 415 participants, urinary levels of these miRNAs were consistently elevated in the CRC group compared to the healthy controls. Notably, the panel of combining miR-129-1-3p and miR-566 revealed an AUC of 0.845 for stage 0/I CRC that can be treated with endoscopic resection.Since noninvasive biomarkers as an alternative to invasive colonoscopy to detect colorectal cancer (CRC) are desired, we conducted this study to determine the urinary biomarker consisting of microRNAs (miRNAs). In total, 415 age- and sex-matched participants, including 206 patients with CRC and 209 healthy controls (HCs), were randomly divided into three groups: (1) the discovery cohort (CRC, n = 3; HC, n = 6); (2) the training cohort (140 pairs); and (3) the validation cohort (63 pairs). Among 11 urinary miRNAs with aberrant expressions between the two groups, miR-129-1-3p and miR-566 were significantly independent biomarkers that detect CRC. The panel consisting of two miRNAs could distinguish patients with CRC from HC participants with an area under the curve (AUC) = 0.811 in the training cohort. This panel showed good efficacy with an AUC = 0.868 in the validation cohort. This urinary biomarker combining miR-129-1-3p and miR-566 could detect even stage 0/I CRC effectively with an AUC = 0.845. Moreover, the expression levels of both miR-129-1-3p and miR-566 were significantly higher in primary tumor tissues than in adjacent normal tissue. Our established novel biomarker consisting of urinary miR-129-1-3p and miR-566 enables noninvasive and early detection of CRC.

Highlights

  • IntroductionColorectal cancer (CRC) is a frequent cause of cancer deaths worldwide [1]

  • Introduction conditions of the Creative CommonsColorectal cancer (CRC) is a frequent cause of cancer deaths worldwide [1]

  • Other studies showed that reduced expression of miR-566 was correlated to colorectal cancer (CRC) development [44] and was involved in epithelial–mesenchymal transition (EMT)

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Summary

Introduction

Colorectal cancer (CRC) is a frequent cause of cancer deaths worldwide [1]. Because early-stage CRC is curable by minimally invasive therapy in many cases, early detection through mass screening is important for reducing mortality. CS screening shows high CRC detection rates and adenomas [2], it has not been widely applied for screening tests due to its invasiveness and high cost. The fecal immunochemical test (FIT) has been established as a widely recommended screening tool to detect CRC [3,4]. It has been reported that 20–40% of CRC, especially stage 0/I CRC, is not detectable by FIT [5–7]. The multitarget stool DNA screening test that detects CRC-related genetic mutations has been developed to detect

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