Liquid Biopsy for Early Detection of Colorectal Cancer Using Circular RNA (CIRCLE)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed 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.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Goel Ajay, PhD
- Phone Number: 626-218-3452
- Email: ajgoel@coh.org
Study Locations
-
-
California
-
Duarte, California, United States, 91016
- Recruiting
- City of Hope Medical Center
-
Contact:
- Ajay Goel, PhD
- Phone Number: 626-218-3452
- Email: ajgoel@coh.org
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
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
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
|
Colorectal Cancer - Training Cohort
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.
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Circular RNA detection in plasma or serum by RT-qPCR
|
|
Non-Disease Control - Training Cohort
Healthy individuals with no prior malignancy or major systemic disease, age- and sex-matched to the CRC group, included in the training set.
|
Circular RNA detection in plasma or serum by RT-qPCR
|
|
Colorectal Cancer - Validation Cohort
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.
|
Circular RNA detection in plasma or serum by RT-qPCR
|
|
Non-Disease Control - Validation Cohort
Independent cohort of healthy participants without malignant or inflammatory bowel disease, serving as external validation controls.
|
Circular RNA detection in plasma or serum by RT-qPCR
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Sensitivity
Time Frame: Through study completion, an average of 1 year
|
Proportion of early-stage (Stage I-II) colorectal cancer patients correctly identified as positive by the circRNA-based diagnostic model.
|
Through study completion, an average of 1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Proportion of correct predictions (true positives and true negatives) among the total cases (i.e., accuracy)
Time Frame: Through study completion, an average of 1 year
|
A measure of trueness: proportion of correct predictions (both true positives and true negatives) among the total number of cases examined
|
Through study completion, an average of 1 year
|
|
Specificity
Time Frame: Through study completion, an average of 1 year
|
True Negative Rate: the probability of a negative test result, conditioned on the individual truly being negative
|
Through study completion, an average of 1 year
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Ajay Goel, PhD, City of Hope Medical Center
Publications and helpful links
General Publications
- Keum N, Giovannucci E. Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nat Rev Gastroenterol Hepatol. 2019 Dec;16(12):713-732. doi: 10.1038/s41575-019-0189-8. Epub 2019 Aug 27.
- Siegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A. Cancer statistics, 2025. CA Cancer J Clin. 2025 Jan-Feb;75(1):10-45. doi: 10.3322/caac.21871. Epub 2025 Jan 16.
- Dong Y, He D, Peng Z, Peng W, Shi W, Wang J, Li B, Zhang C, Duan C. Circular RNAs in cancer: an emerging key player. J Hematol Oncol. 2017 Jan 3;10(1):2. doi: 10.1186/s13045-016-0370-2.
- Qu S, Yang X, Li X, Wang J, Gao Y, Shang R, Sun W, Dou K, Li H. Circular RNA: A new star of noncoding RNAs. Cancer Lett. 2015 Sep 1;365(2):141-8. doi: 10.1016/j.canlet.2015.06.003. Epub 2015 Jun 5.
- Jeck WR, Sharpless NE. Detecting and characterizing circular RNAs. Nat Biotechnol. 2014 May;32(5):453-61. doi: 10.1038/nbt.2890.
- Chen LY, Wang L, Ren YX, Pang Z, Liu Y, Sun XD, Tu J, Zhi Z, Qin Y, Sun LN, Li JM. The circular RNA circ-ERBIN promotes growth and metastasis of colorectal cancer by miR-125a-5p and miR-138-5p/4EBP-1 mediated cap-independent HIF-1alpha translation. Mol Cancer. 2020 Nov 23;19(1):164. doi: 10.1186/s12943-020-01272-9.
- Xu H, Liu Y, Cheng P, Wang C, Liu Y, Zhou W, Xu Y, Ji G. CircRNA_0000392 promotes colorectal cancer progression through the miR-193a-5p/PIK3R3/AKT axis. J Exp Clin Cancer Res. 2020 Dec 14;39(1):283. doi: 10.1186/s13046-020-01799-1.
- Long F, Lin Z, Li L, Ma M, Lu Z, Jing L, Li X, Lin C. Comprehensive landscape and future perspectives of circular RNAs in colorectal cancer. Mol Cancer. 2021 Feb 3;20(1):26. doi: 10.1186/s12943-021-01318-6.
- Zhang Y, Luo J, Yang W, Ye WC. CircRNAs in colorectal cancer: potential biomarkers and therapeutic targets. Cell Death Dis. 2023 Jun 9;14(6):353. doi: 10.1038/s41419-023-05881-2.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 23228/CIRCLE
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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