Transcriptome-based inference of immune cell subsets and pathway deregulation in rectal cancer reveals biological processes related to therapy response

JUAN MARTÍN SENDOYA; SOLEDAD ISEAS; MARIANO GOLUBICKI; JUAN ROBBIO; MARIANA CORAGLIO; UBALDO GUALDRINI; ANA CABANNE; MIRTA KUJARUK; VANESA MIKOLAITIS; MARIANA RIZZOLO; RUBEN SALANOVA; CECILIA ROTONDARO; MARTIN C. ABBA; OSVALDO LUIS PODHAJCER; ENRIQUE ROCA; ANDREA LLERA

Chicago

Congreso; 109th Annual Meeting of the American Association for Cancer Research; 2018

Purpose: Colorectal cancer is the second most frequent cancer and the second and third cause of cancer-related mortality in Argentina for men and women respectively. For locally advanced rectal cancer (LARC), preoperative chemoradiotherapy (CRT) ± induction chemotherapy (iCT) comprises the standard treatment. However, only 15-27% of patients achieve a pathological complete response, while 40-60% respond variably. This scenario poses a strong need for biomarkers able to predict response to CRT and provide guidance towards optimal treatment for each patient. Here we explore LARC gene expression data to identify baseline immune populations and pathways that might be associated with response to CRT.Methods: Using Agilent Human Genome Microarrays, we analyzed gene expression in pre-treatment tumor biopsies of 26 LARC patients as part of an ongoing prospective translational study in Argentina. After treatment with CRT (capecitabine + radiotherapy) ± iCT (capecitabine + oxaliplatin) and surgery, pathological response was assessed according to College of American Pathologists (CAP) guidelines. We grouped CAP scores 0-1 as responders and 2-3 as nonresponders. We estimated cellular heterogeneity of the microenvironment from transcriptomic data by applying two independent computational methods: GSVA and xCell, and inferred patient-specific pathway deregulation with PARADIGM. To elucidate differential features between both patient groups, we performed Two-sample t-Tests for GSVA and xCell, and Rank Product test for PARADIGM. All tests were adjusted for FDR