Dissecting the Biology of Early-onset Colorectal Cancer

Contrarily to late-onset (LO) colorectal cancer (CRC), early-onset (EO) CRC incidence is increasingly growing. Several factors, such as obesity, chronic inflammation, and intestinal dysbiosis, can increase the general risk of CRC. However, little is known about the biology of EO-CRC. To evaluate whether such selective rise in the incidence of EO-CRC patients mirrors a distinct transcriptomic profile, the investigators will first dissect EO-CRC’s transcriptomic landscape.
Then, the investigators will investigate the colorectal cancer stem cell (CSC) compartment by in vitro functional assays and RNA-seq analysis. Because our preliminary data indicate an increased aggressiveness of the tumor microenvironment (TME) in EO-CRC,the investigators propose to investigate the CSC niche and the interaction with the TME to dissect the molecular and cellular pathways occurring in EO-CRC.
A cohort of 30 EO-CRC patients (<50 years old) will be enrolled and fully characterized. About 10 EO-CRC-derived CSCs in the form of organoids and spheroids will be generated. Since the relevant differences between CR-CSCs isolated from EO-CRC vs LO-CRC patients are still unknown, the investigators will gain information about their specific features such as clonogenic activity, tumorigenic/invasive capacity, and about differences in the mechanisms regulating their cross-talk with TME components.