Analysis of A 6-Mirna Signature in Serum from Colorectal Cancer Screening Participants as Non-Invasive Biomarkers for Advanced Adenoma and Colorectal Cancer Detection

Abstract

Early detection of colorectal cancer (CRC) and its precancerous lesion, advanced adenomas (AA), is critical to improve CRC incidence and prognosis. Circulating microRNAs (miRNAs or miR) are promising non-invasive biomarkers for cancer detection. Our previous results showed that a plasma 6-miRNA signature (miR-15b-5p, miR-18a-5p, miR-29a-3p, miR-335-5p, miR-19a-3p and miR-19b-3p) could distinguish between CRC or AA and healthy individuals (controls). However, its diagnostic performance in serum is unknown. In this exploratory study we aim to evaluate the diagnostic performance of the 6-miRNA signature in serum samples in a cohort of individuals participating in Barcelona’s CRC Screening Programme. We prospectively collected serums from 264 faecal immunochemical test (FIT)-positive participants and total RNA was extracted. Finally, 213 individuals (CRC, 59, AA, 74, controls, 80) were included. MiRNA expression was quantified by real-time RT-qPCR and data analysis was performed by logistic regression. Faecal hemoglobin concentration (f(Hb)) from FIT of the same individuals was also considered. As previously described in plasma, serum from patients with AA or CRC presented significant differences in the 6-miRNA signature compared to controls. Moreover, when combined with f(Hb), the final signature showed high discriminative capacity to distinguish CRC from controls (area under the curve (AUC) = 0.88), and even AA (AUC = 0.81) that otherwise are poorly detected if we only consider f(Hb) (AUC = 0.64). Addition of the serum 6-miRNA signature to quantitative f(Hb) show high accuracy to detect patients with advanced colorectal neoplasia in average-risk individuals. A combination of these two non-invasive methods could be a good strategy to improve diagnostic performances of current CRC screening programmes.

miRNAs-Based Molecular Signature for KRAS Mutated and Wild Type Colorectal Cancer: An Explorative Study

“…In CRC, this miRNA has been suggested as potential therapeutic target for CRC treatment, particularly for 5-FU-resistant CRC [ 48 ] and potential target for metastatic CRC therapy [ 49 ]. Also, its levels could be useful to distinguish between CRC or its precancerous lesion (advanced adenomas) and healthy individuals controls [ 50 ]. MiR-98-5p levels have been found dysregulated in different types of cancer cells, such as nonsmall cell lung carcinoma [ 51 ], prostate cancer [ 52 ], and breast cancer [ 53 ].…”

A three-miRNA panel in serum as a noninvasive biomarker for colorectal cancer detection

“…An increasing number of studies have demonstrated that circulating miRNAs are able to act as diagnostic biomarkers in a variety of cancers. 10,11 In fact, several previous studies have identified some circulating miRNA biomarkers for the diagnosis of CRC [12][13][14] ; however, more research and evidence are required before their clinical use.…”

Liquid Biopsy is Instrumental for 3PM Dimensional Solutions in Cancer Management

“…Additionally, Du et al have indicated that an analysis of a combination of squamous cell carcinoma antigen (SCC Ag) degree and miRNA-29a, miRNA-25, miRNA-486-5p levels in serum could improve the detection of early-stage cervical cancer [ 98 ]. Moreover, an evaluation of serum signature of six miRNAs (miR-15b-5p, miR-29a-3p, miR-335-5p, miR-18a-5p, miR-19a-3p, and miR-19b-3p) and fecal hemoglobin concentration has revealed high accuracy of the detection of advanced colorectal neoplasia in average-risk individuals [ 146 ].…”