Integrative (genomic, transcriptomic and methylome) analyses of rectal cancer to unravel predictors of neoadjuvant treatment response

Abstract

Stage II-III rectal carcinoma (ReCa) patients undergo neoadjuvant chemoradiotherapy (nCRT) followed by surgery. Those who achieve pathological complete response (pCR) have better prognosis and could be spared of a highly morbid procedure if pCR was accurately identified precociously. However, the current molecular studies have shown inconclusive results. Our study aims to evaluate the genomic methylation profile of ReCa biopsies of patients that underwent nCRT and integrate the data with copy number and expression profiles from the same patients (data already obtained). The methylation profile will be obtained using a Platform from Illumina (450K), which provides methylation status of 96% of the CpG islands described. This project will be performed under the supervision of Dr. Rogatto, whose laboratory has an excellent infrastructure, well equipped to perform methylation experiments and analysis. Integration of omics data will be developed in collaboration with Dr. Jan Baumbach, who has an extensive experience in computational systems biomedicine research. The suggested project perfectly fits Baumbach's expertise in the combined analysis of multiple omics data types together with biochemical networks. It will prove particularly useful for unraveling new biomarkers allowing stratification of therapy, helping to recognize nCRT-sensitive patients and reducing the rate of postoperative morbidity. A comprehensive analysis of genetic and epigenetic alterations of rectal tumors from patients undergoing nCRT and its putative correlation to treatment response has the potential to identify molecular drivers useful for clinical practice. (AU)