Liquid Biopsy for Early Detection of Colorectal Cancer Using Circular RNA (CIRCLE)

City of Hope

Status: Enrolling

Conditions: Colorectal Cancer

Treatments: Diagnostic Test: cf-circRNA assay

Study type: Observational

Funder types: Other

Identifiers

NCT07224789

23228/CIRCLE

Details and patient eligibility

About

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. This study aims to develop a non-invasive liquid biopsy assay using plasma-derived cell-free circular RNAs (cf-circRNAs) for early and accurate detection of colorectal cancer.

Full description

Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer-related mortality worldwide. Despite the proven benefit of screening colonoscopy, its invasive nature, high cost, and low adherence rates limit its use for population-level early detection. Current non-invasive screening tools, such as fecal occult blood testing and stool DNA assays, offer limited sensitivity, particularly for early-stage or right-sided colorectal tumors.

Therefore, there is a growing clinical need for a highly sensitive, minimally invasive, and patient-compliant diagnostic approach that can complement existing screening modalities.

Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNAs characterized by covalently closed loop structures formed through back-splicing. Unlike linear RNAs, circRNAs are resistant to exonuclease-mediated degradation and are remarkably stable in body fluids. They exhibit tissue- and cancer-specific expression patterns, suggesting strong potential as non-invasive biomarkers.

Emerging evidence demonstrates that cell-free circRNAs (cf-circRNAs) circulate in plasma or serum either freely or encapsulated within extracellular vesicles such as exosomes. These cf-circRNAs retain the molecular signatures of their tumor of origin and can be reliably quantified using reverse transcriptase-quantitative PCR (RT-qPCR) or next-generation sequencing (NGS)-based platforms.

The CIRCLED study (Circular RNA for Colorectal Cancer Detection) is designed as a multi-center, case-control, observational study aiming to (1) identify diagnostic circRNA candidates from RNA sequencing, and (2) validate a cf-circRNA diagnostic panel capable of differentiating CRC patients from healthy individuals and those with benign colorectal diseases.

Enrollment: 600 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Adults (≥18 years old)
• Histologically confirmed colorectal cancer (Stage I-III)
• Availability of pre-treatment plasma samples
• Written informed consent provided

Exclusion criteria

• History of other active malignancies within the past 5 years
• Poor sample quality or hemolysis
• Inability to provide informed consent

Trial design

600 participants in 4 patient groups

Colorectal Cancer - Training Cohort

Description:

Patients with histologically confirmed colorectal adenocarcinoma (Stage I-III) enrolled in the training set. Plasma samples are collected before any surgery or therapy for cf-circRNA profiling.

Treatment:

Diagnostic Test: cf-circRNA assay

Non-Disease Control - Training Cohort

Description:

Healthy individuals with no prior malignancy or major systemic disease, age- and sex-matched to the CRC group, included in the training set.

Treatment:

Diagnostic Test: cf-circRNA assay

Colorectal Cancer - Validation Cohort

Description:

Independent cohort of patients with histologically confirmed colorectal adenocarcinoma (Stage I-III) from separate institutions, used to validate the diagnostic cf-circRNA signature. Plasma obtained prior to treatment.

Treatment:

Diagnostic Test: cf-circRNA assay

Non-Disease Control - Validation Cohort

Description:

Independent cohort of healthy participants without malignant or inflammatory bowel disease, serving as external validation controls.

Treatment:

Diagnostic Test: cf-circRNA assay