Serum miR-21, miR-29a, and miR-125b Are Promising Biomarkers for the Early Detection of Colorectal Neoplasia

Abstract

Purpose Circulating microRNAs (miRNAs) are emerging as promising diagnostic biomarkers for colorectal cancer (CRC), but their usefulness for detecting early colorectal neoplasms (CRNs) remains unclear. This study aimed to identify serum miRNA biomarkers for the identification of patients with early CRNs. Experimental Design A cohort of 237 serum samples from 160 patients with early CRNs (148 precancerous lesions and 12 cancers) and 77 healthy subjects was analyzed in a three-step approach that included: a comprehensive literature review for published biomarkers, a screening phase, and a validation phase. RNA was extracted from sera, and levels of miRNAs were examined by real-time RT-PCR. Results Nine miRNAs (miR-18a, miR-19a, miR-19b, miR-20a, miR-21, miR-24, miR-29a, miR-92 and miR-125b) were selected as candidate biomarkers for initial analysis. In the screening phase, serum levels of miR-21, miR-29a and miR-125b were significantly higher in patients with early CRN compared to healthy controls. Elevated levels of miR-21, miR-29a and miR-125b were confirmed in the validation phase using an independent set of subjects. Area under the curve (AUC) values for serum miR-21, miR-29a, miR-125b, and their combined score in discriminating early CRN patients from healthy controls were 0.706, 0.741, 0.806 and 0.827 respectively. Serum levels of miR-29a and miR-125b were significantly higher in patients who only had small CRNs (≤5mm) compared to healthy subjects. Conclusions Since serum levels of miR-21, miR-29a and miR-125b discriminated early CRN patients from healthy controls, our data highlight the potential clinical use of these molecular signatures for noninvasive screening of patients with colorectal neoplasia.

Circulating Exosomal MicroRNA-21 as a Biomarker in Each Tumor Stage of Colorectal Cancer

“…Recently, several papers have reported the usefulness of plasma/serum miR-21 levels as a biomarker for diagnosis in CRC patients [23,24,25,26,27,28]. However, the clinical significance of plasma/serum miRNA as a biomarker for diagnosis is still controversial, and some papers have indicated that serological miR-21 does not have any impact on diagnosis in CRC patients [29,30].…”

A panel of microRNA signature in serum for colorectal cancer diagnosis

“…A few recent studies have revealed the diagnostic role of circulating miRNAs in CRC [13, 14, 18]. Unfortunately, to date, independent studies have failed to develop clinically actionable miRNA biomarkers for a variety of reasons including population and sample diversity, especially the discovery and validation methodologies used in these reports.…”

“…Numerous studies have demonstrated that miRNAs can be stably detected in serum or plasma and have the potential to be new biomarkers for early diagnosis of various types of cancers [9–12]. Additionally, several studies have revealed that some miRNAs are able to discriminate CRC patients from healthy controls and serve as serum biomarkers for CRC screening with high accuracy [13, 14]. However, these results lack consistencies because of different research methods and tested populations between laboratories.…”

miR-125b is associated with renal cell carcinoma cell migration, invasion and apoptosis

“…In colorectal cancer (CRC), the expression of miR-125b was downregulated (32), while in patients with early colorectal neoplasia (including precancerous lesions and early CRCs) the expression of serum miR-125b was also upregulated compared with healthy controls. Therefore, miR-125b may be used as biomarker for early detection of colorectal neoplasia (33). Thus, the expression of miR-125b in different stages of tumors varies, indicating that the role of miR-125b is constantly changing during the tumorigenesis.…”