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Dissecting the Biology of Early-onset Colorectal Cancer

Not yet recruiting
Conditions
Colon Cancer
Registration Number
NCT05916443
Lead Sponsor
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
30
Inclusion Criteria
  • age > 18 and < 50 years ;
  • Written informed consent
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Exclusion Criteria
  • Non-availability of informed consent.
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Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Isolation and characterization of EO-CRC-derived CSCs2 years

Identification of EO-CRC-derived CSCs by cytofluorimetry and immunofluorescence analyses (Percentage of cells positive for CD133, CD24, CD44 and CD44v6 expression).

Identification of EO-CRC specific signatures and pathways2 years

RNAseq data analysis of differentially expressed genes in EO-CRC-derived CSCs compared with LO-CRC-derived CSCs.

Identification of obesity-associated adipokines in EO-CRC obese patients2 years

Elisa/Luminex assay evaluation of obesity-associated adipokines concentration

Secondary Outcome Measures
NameTimeMethod
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