NCT03127111

Genetic and Epigenetic Determinants of Response to Fluorouracil-based Adjuvant Chemotherapy in Patients With Stage III Colorectal Cancer

The Identification, Validation and Implementation of Molecular Markers to Predict Response to Fluorouracil-based Adjuvant Chemotherapy in Stage III Colorectal Cancer Patients - Prospective Clinical Observational Study

• Status: Not Yet Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 300 (estimated)
• Sponsor: Renmin Hospital of Wuhan University · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Accepted

Summary

The goal of this laboratory research is to look for genetic and epigenetic markers that can predict which patients with stage III colorectal cancer will benefit from fluorouracil-based adjuvant chemotherapy.

Detailed description

This is a prospective project in collecting and assessing clinical outcomes data related to molecular profiling of tumors based on samples from peripheral blood, primary tumor, and adjacent normal colorectal tissue. Objectives: 1. Validation of predictive value of known markers CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) in the response to 5-fluorouracil-based chemotherapy in patients with stage III colorectal cancer. 2. Exploratory evaluation of the potential predictive values of known genetic variations including, but not limited to, KRAS mutations, BRAF mutations, PIK3A mutations, and EGFR mutations, etc. 3. Exploratory identification and evaluation of the predictive value of novel methylation aberrations identified by whole-genome bisulfite sequencing. 4. Exploratory identification and evaluation of the predictive value of novel genetic aberrations discovered by RNA-sequencing (RNA-seq) or genome-wide association study (GWAS). Outline: Blood is collected at baseline and examined for single-nucleotide polymorphisms (SNPs) and expression level of specific gene. Tumor and corresponding normal tissue at surgical resection and assessed for gene methylations, mutations, and expressions.

Conditions

• Stage III Colorectal Cancer

Interventions

Type	Name	Description
GENETIC	Gene mutations analysis	Genomic DNA extracted from paired fresh-frozen tumor and normal tissues is used for KRAS mutations, BRAF mutations, PIK3A mutations, and EGFR mutations, etc., by sequencing and for MSI analysis by PCR and capillary electrophoresis.
GENETIC	Gene methylation analysis	Genomic DNA extracted from paired fresh-frozen tumor and normal tissues is used for specific gene methylation or CIMP status analysis by MethyLight or bisulfite sequencing. Whole-genome bisulfite sequencing will be used to identify novel candidate set of predictive markers.
GENETIC	Gene expression analysis	RNA extracted from paired fresh-frozen tumor and normal tissues or serum is used for specific gene expression analysis by real-time reverse-transcription PCR (RT-qPCR). RNA-seq will be used to identify novel candidate set of predictive markers.
GENETIC	SNP analysis	Genomic DNA extracted from serum is used for specific SNP analysis by using sequencing. GWAS with SNPs array will be used to identify novel candidate set of predictive markers.
GENETIC	Protein expression analysis	Tissue microarray made from formalin-fixed paraffin-embedded (FFPE) paired tumor and normal tissues is used for specific protein expression analysis by immunohistochemistry staining.

Timeline

• Start date: 2022-12-01
• Primary completion: 2025-12-31
• Completion: 2026-12-31
• First posted: 2017-04-25
• Last updated: 2022-03-15

Locations

1 site across 1 country: China