Plasma MicroRNA Signature Validation for Early Detection of Colorectal Cancer

Abstract

OBJECTIVES: Specific microRNA (miRNA) signatures in biological fluids can facilitate earlier detection of the tumors being then minimally invasive diagnostic biomarkers. Circulating miRNAs have also emerged as promising diagnostic biomarkers for colorectal cancer (CRC) screening. In this study, we investigated the performance of a specific signature of miRNA in plasma samples to design a robust predictive model that can distinguish healthy individuals from those with CRC or advanced adenomas (AA) diseases. METHODS: Case control study of 297 patients from 8 Spanish centers including 100 healthy individuals, 101 diagnosed with AA, and 96 CRC cases. Quantitative real-time reverse transcription was used to quantify a signature of miRNA (miRNA19a, miRNA19b, miRNA15b, miRNA29a, miRNA335, and miRNA18a) in plasma samples. Binary classifiers (Support Vector Machine [SVM] linear, SVM radial, and SVM polynomial) were built for the best predictive model. RESULTS: Area under receiving operating characteristic curve of 0.92 (95% confidence interval 0.871–0.962) was obtained retrieving a model with a sensitivity of 0.85 and specificity of 0.90, positive predictive value of 0.94, and negative predictive value of 0.76 when advanced neoplasms (CRC and AA) were compared with healthy individuals. CONCLUSIONS: We identified and validated a signature of 6 miRNAs (miRNA19a, miRNA19b, miRNA15b, miRNA29a, miRNA335, and miRNA18a) as predictors that can differentiate significantly patients with CRC and AA from those who are healthy. However, large-scale validation studies in asymptomatic screening participants should be conducted.

MiR-3622a-3p acts as a tumor suppressor in colorectal cancer by reducing stemness features and EMT through targeting spalt-like transcription factor 4

“…There were still several limitations to our study. Circulating miRNAs have been reported to function as biomarkers for early detection of CRC [47]. However, the expression level of miR-3622a-3p was only detected in tissue samples rather than plasma specimens.…”

MiR-3622a-3p acts as a tumor suppressor in colorectal cancer by reducing stemness features and EMT through targeting spalt-like transcription factor 4

“…There were still several limitations to our study. Circulating miRNAs have been reported to function as biomarkers for early detection of CRC 50 . However, the expression level of miR-3622a-3p was only detected in tissue samples rather than plasma specimens.…”

Whole-blood DNA Methylation Markers for Risk Stratification in Colorectal Cancer Screening: A Systematic Review

“…Compared to methylation of SEPT9 [22,23] in tumor-derived cell-free DNA, or to other types of molecular markers such as micro RNA [60,61], genetic [62], or proteomic markers [63,64], performance of whole-blood methylation markers for diagnosis/risk stratification of colorectal neoplasms seems much poorer. In the past 10–15 years large progress has been made in risk stratification of CRC by genetic risk variants and their combination in polygenetic risk scores [62,65,66,67,68].…”