COMPREHENSIVE TRANSCRIPTOMIC ANALYSIS FOR THE IDENTIFICATION OF LONG NON-CODING RNAs (LncRNAs) WITH CLINICAL IMPLICATIONS IN THE MOLECULAR SUBTYPES OF COLORECTAL CANCER.

EZEQUIEL LACUNZA

Congreso; REUNIÓN CONJUNTA SAIC SAI&FAIC SAFIS 2022; 2022

Colorectal cancer (CRC) is a frequently lethal disease with heterogeneous prognosis and response to treatment. Most CRC progress from normal epithelium, through a benign precursor adenoma, through the accumulation of genetic alterations in oncogenes and tumor suppressor genes, and additional epigenetic aberrations implicated in disease initiation and progression. Multi-omics studies have revealed the transcriptional landscape of CRC, allowing patients to be classified according to 4 consensus molecular subtypes (CMS1-4). CMS1-immune comprises the majority of tumors with microsatellite instability (MSI) and is characterized by the infiltration of activated immune cells. CMS2-canonical and CMS3-metabolic show epithelial features, with high WNT and MYC signaling predominantly in CMS2 and metabolic reprogramming in CMS3. CMS4 comprises the most similar cancers to mesenchymal ones, with high stromal infiltration and poor patient prognosis. The clinical utility of the CMS classification resides in the possibility to estimate survival (prognostic value) and select patients for both chemotherapy and currently used targeted agents (predictive value). Long non coding RNAs (LncRNAs) are defined as RNAs that do not code for proteins and exceed 200 nucleotides in length. LncRNAs play key roles in the regulation of chromatin dynamics, gene expression, epigenetic regulation, growth, and differentiation. An increasing number of studies have demonstrated the aberrant expression of LncRNAs in human cancers, assigning them a promising role as diagnostic and prognostic biomarkers. The deregulation of LncRNAs has been shown to be closely related to the development and progression of CRC. Currently, there are no LncRNA signatures that are distinctive of precancerous CRC lesions or of the molecular subtypes that define tumors. The lecture will go over these topics, followed by a comprehensive transcriptomic bioinformatics analysis for the identification of clinically relevant LncRNA signatures in the context of the CMS classification of CRC in premalignant lesions and tumors. These repertoires of LncRNAs could be evaluated in screening colonoscopy biopsies and plasma samples from patients in order to consider them as specific molecular tools that may have diagnostic, prognostic and/or predictive value