Comprehensive clinical, pathological and molecular characterization of a cohort of locally advanced rectal cancer patients: Towards an integrative classification for rectal cancer management.

SENDOYA, JUAN M.; ISEAS, SOLEDAD; GOLUBICKI, MARIANO; CORAGLIO, MARIANA; GUALDRINI UBALDO; CABANNE ANA; KUJARUK MIRTA; MIKOLAITIS VANESA; RIZZOLO MARIANA; SALANOVA RUBEN; ROTONDARO, CECILIA; FERNANDEZ ELMER; PODHAJCER OSVALDO; ROCA ENRIQUE; LLERA ANDREA

Buenos Aires

Congreso; Segunda Reunión Conjunta de Sociedades de BioCiencias; 2017

Sociedad Argentina de Investigaciones Clínicas

Introduction: Locally Advanced Rectal Cancer (LARC) response to preoperative chemoradiotherapy (CRT) is very heterogeneous. Current prognosis-related factors lack robustness to individualize therapeutic decisions. Four Consensus Molecular Subtypes (CMS) represent the current best description of colorectal cancer heterogeneity at the gene expression level. We aim to integrate CMS predictions with available clinical data from an Argentinian LARC cohort in search of biomarkers to improve patient management. Methods: We analyzed gene expression in baseline tumor biopsies of the first 24 LARC patients from an ongoing recruiting translational research trial. Mutations in RAS and BRAF were measured by PCR Entrogen panel. DNA repair proteins(MLH1,MSH2,MSH6,PMS2) were measured by Cell Marquemonoclonal primary antibodies. Gene expression data was obtained using Agilent Agi4x44K Whole Human Genome microarrays, and CMS-classified with the R package ?CMSclassifier? using a similarity-to-centroid approach. Results: Subtype classification showed CMS2-Canonical subtype patients (79%) of which one showed MSH2 gene and protein expression deficit, and one carried KRAS G12A mutation; CMS3-Metabolic (13%) with one KRAS-mut patient; CMS1-MSI immune (4%) diagnosed Lynch Syndrome confirmed by a germinal MSH2 mutation; CMS4-Mesenchymal (4%) showing higher stromal gene expression. Conclusion: To our knowledge, this is the first classification of local LARC patients into descripted colorectal molecular subtypes combining prospective clinical and genomic data to enrich patient characterization. We expect that future analyzed cases from this ongoing trial might help us establish further molecular features to correlate with CRT response.