Title of Presentation
“Workflow for the identification and validation of microRNAs: the colorectal cancer experience”
Date and Place
Dr. Paolo Verderio is currently senior researcher at the Fondazione IRCCS Istituto Nazionale dei Tumori (INT) of Milan. At INT, he is team leader of “Biostatistics for Oriented Basic Research and Quality Control” at the Unit of Medical Statistics, Biometry and Bioinformatics since 2007 and member of the “Organismo Preposto al Benessere degli Animali” since 2014. His main activities are focused on the statistical-methodological aspects related to the implementation and statistical analysis of studies for setting-up and validation of new biological assays for biomarkers identification as well as quality control studies for tumor biomarkers and in-vitro diagnostic tools. He was partner of the FP7-EU SPIDIA Project and of other project at national (Integrated Program in Oncology) and international level (FP6-EU EQUAL). Currently, his main research activity is focused on the design and statistical analysis of studies aimed at identifying and validating oncology biomarkers of potential clinical relevance.
MiRNAs are promising non invasive diagnostic biomarkers that can be easily detected in plasma. However, several factors, both pre-analytical and analytical, must be taken into account during the identification and validation of miRNA biomarkers.The workflow for the identification of a biomarker should start with a discovery phase, ideally based on high-throughput technologies to identify candidate biomarkers that will be further investigated in the subsequent validation phases.The discovery phase should also allow the setting-up of all the aspects of the pre-analytical phase of sample collection/processing and the pre-processing steps of the data, such as data normalization.During validation phase(s) the performance of the candidate biomarkers should be adequately explored using advanced statistical methodologies to identify powerful miRNA-based signatures. Assay-oriented step(s) may be included in the workflow to set-up new assays easy transferable to the clinical setting. In this workflow the availability of stored material could be of help in the biomarker development pipeline. As part of the ongoing EDERA project (http://www.ederaproject.it) at Istituto Nazionale Tumori (INT), we applied the described workflow for the identification and validation of miRNAs for the early detection of colorectal cancer, using individuals positive to the fecal occult blood test as target population. The discovery phase was performed on retrospective plasma samples stored in our biobank; miRNAs profiling was done using the TaqMan® Array Human MicroRNA Card A (Applied Biosystems). The validation phase consisted of two phases based on plasma samples prospectively collected at INT and during a multi-centric study.