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Individuals who underwent colonoscopy and were found not to have any adenomas or cancer.

Individuals who underwent colonoscopy and were found to only have low-risk adenomas, defined as all of the following:

* 1 or 2 adenomas at most.
* All adenomas have low-grade dysplasia at most.
* All adenomas are \<10 mm in diameter.
* All adenomas are tubular

Individuals who underwent colonoscopy and were found to have high-risk adenomas, defined as one or more of the following:

* 3 or more adenomas.
* One or more adenomas have high-grade dysplasia.
* One or more adenomas are \>10 mm in diameter.
* One or more adenomas are villous

Individuals who underwent colonoscopy and were found to have colorectal cancer.

Individuals who underwent colonoscopy and were found to only have low-risk adenomas, defined as:

* 1 or 2 adenomas at most.
* All adenomas have low-grade dysplasia at most.
* All adenomas are \<10 mm in diameter.
* All adenomas are tubular

A panel of circulating microRNA, whose expression level is tested in cell-free and exosome-derived samples.

DENEB

Ajay Goel, PhD

Caiming Xu

Alessandro Mannucci

James Lin

Gregory Idos

Trilokesh Kadambi

C Richard Boland, MD, PhD

Jing Zhang

Giulia Martina Cavestro, MD, PhD

Giulia Martina Cavestro

Yuji Toiyama

Yoshinaga Okugawa

Tadanobu Shimura

Francesc Balaguer, MD, PhD

Francesc Balaguer

Miguel Pera

Lorena Moreno

Luis Bujanda

This study aims to develop a highly sensitive, specific, and cost-effective blood assay for early detection of colorectal adenomas and cancer, using advanced machine learning and state-of-the-art biological analyses.

Colorectal cancer (CRC) is a significant global health concern, ranking third in diagnosis and second in mortality. Despite being potentially preventable, it remains a leading cause of cancer-related deaths. Traditional screening methods like fecal immunochemical testing (FIT) have shown benefits in reducing late-stage diagnoses but have not effectively prevented CRC incidence. This is because tests like FIT can effectively detect the cancers, but not the precursor lesions, called adenomas. On the other hand, endoscopy-first approaches offer higher sensitivity for such adenomas and, therefore, lower the risk of developing CRC but face challenges such as invasiveness, cost, and patient compliance.

Non-invasive tests are more appealing to patients than invasive tests and can increase participation rates. Biomarker studies have shown promise, but existing tests lack sensitivity for early-stage CRC and advanced adenomas (AAs). This is likely because they assume the same analyte can detect both CRC and AAs, which may not be accurate due to differences in analyte release and the biological changes that occur during the adenoma-carcinoma sequence.

This study proposes developing an innovative liquid biopsy test tailored for AAs and CRC to address this. An ideal screening test should be minimally invasive, highly sensitive, and cost-effective. This test would optimize patient compliance and resource allocation by detecting both conditions from a single blood draw. More specifically, circulating microRNA (miRNA) analysis shows promise: tests based on cell-free microRNA (cf-miRNA) have demonstrated high sensitivity, while those based on exosome-derived microRNA (exo-miRNA) offer high specificity. Therefore, combining both analytes in a single test could maximize sensitivity and specificity.

This study will develop a non-invasive blood test for AA and CRC in four phases:

1. Genome-wide profiling of cf-miRNA and exo-miRNA and selecting the best candidates for biomarker panels.
2. Utilizing machine learning to identify promising candidates and train algorithms for detecting AAs and CRC separately, based on results from quantitative polymerase chain reaction (qPCR) analysis.
3. Combining these algorithms to create detection signatures for both conditions.
4. Independently validating these signatures using diverse cohorts to ensure broad applicability and compare the effectiveness of the blood assay to standard care through retrospective and prospective studies.

This study aims to develop a highly sensitive, specific, and cost-effective liquid biopsy for early detection of AAs and CRC. Success could transform clinical practice by preventing CRC through early detection of pre-malignant lesions. Innovations include incorporating pre-malignant lesions into screening and combining cf-miRNA and exo-miRNA biomarkers for accuracy. This approach could reduce CRC mortality and incidence and pave the way for new clinical trials.

Early Detection of Advanced Adenomas and Colorectal Cancer

A Liquid Biopsy Assay For The Non-Invasive Early Detection of Advanced Adenomas and Colorectal Cancer

Data collected for the study will be made available to others, including de-identified participant data, at publication, via a signed data access agreement and at the discretion of the investigators' approval of the proposed use of such data.

True positive rate: the probability of a positive test result, conditioned on the individual truly being positive

True negative rate: the probability of a negative test result, conditioned on the individual truly being negative

A measure of trueness: proportion of correct predictions (both true positives and true negatives) among the total number of cases examined

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Early Detection of Advanced Adenomas and Colorectal Cancer	NCT06342440	Colorectal Canc... Colorectal Neop... Colorectal Poly... Colorectal Aden... Colorectal Diso... Colorectal Dysp... Colorectal Canc... Colorectal Canc... Colorectal Canc... Colorectal Canc... Colorectal Neop... Colorectal Serr... Colorectal Aden... Colorectal Aden... Colorectal Aden... Colorectal Aden... Colorectal Aden... Colorectal Aden...	DENEB	18 Years -	City of Hope Medical Center
Early Detection of Advanced Adenomas and Colorectal Cancer	NCT06342440	Colorectal Canc... Colorectal Neop... Colorectal Poly... Colorectal Aden... Colorectal Diso... Colorectal Dysp... Colorectal Canc... Colorectal Canc... Colorectal Canc... Colorectal Canc... Colorectal Neop... Colorectal Serr... Colorectal Aden... Colorectal Aden... Colorectal Aden... Colorectal Aden... Colorectal Aden... Colorectal Aden...	DENEB	18 Years -	City of Hope Medical Center
Early Detection of Advanced Adenomas and Colorectal Cancer	NCT06342440	Colorectal Canc... Colorectal Neop... Colorectal Poly... Colorectal Aden... Colorectal Diso... Colorectal Dysp... Colorectal Canc... Colorectal Canc... Colorectal Canc... Colorectal Canc... Colorectal Neop... Colorectal Serr... Colorectal Aden... Colorectal Aden... Colorectal Aden... Colorectal Aden... Colorectal Aden... Colorectal Aden...	DENEB	18 Years -	City of Hope Medical Center

Spots Global Cancer Trial Database for colorectal serrated adenocarcinoma