TORONTO, October 26, 2021 – Early detection of colorectal cancer (CRC) is important for improving the survival rate and life quality of patients. However, the performances of current CRC early detection methods are still limited. Geneseeq and Shanghai Fudan University Cancer Center published a prospective study in the Journal of Hematology & Oncology applying Geneseeq’s MERCURY technology, a novel multi-dimensional fragmentomics approach, to demonstrate a powerful ability to detect the early-stage CRC (stage 0/I) and advanced colorectal adenoma (advCRA). This is by far the largest cohort study conducted on stage 0/I CRC early detection by liquid biopsy.

In this study, an ensemble stacked model differentiating advCRA/early-stage CRC patients  from healthy controls was first trained using a training cohort containing 149 early-stage (stage 0/I) CRC patients, 46 advCRA patients and 115 healthy controls. Plasma samples were collected from the participants followed by cell-free DNA (cfDNA) extraction and low-coverage whole-genome sequencing. Five cfDNA fragmentomics features, including fragment size ratio (FSR), fragment size distribution (FSD), end motif (EDM), breakpoint motif (BPM), and copy number variation (CNV), were then extracted and employed by the ensemble stacked model incorporating five machine learning algorithms. The established model was subsequently validated using an independent testing cohort (N = 311; including 149 early-stage CRC, 46 advCRA and 116 healthy controls), outperforming models with a single cfDNA feature or single algorithm.

Promisingly, the model showed an area under the curve (AUC) of 0.988 for differentiating advCRA/early-stage CRC patients from healthy individuals in the testing cohort, while performing even better for identifying early-stage CRC (AUC 0.990) compared to advCRA (AUC 0.982). At 95% specificity, the sensitivities for detecting advCRA and early-stage CRC reached 95.7% and 98.0% (stage 0: 94.1%; stage I: 98.5%), respectively. When tested in early-stage CRC patients with negative fecal occult or CEA blood test results, the model showed sensitivities of 100% and 97.6%, respectively. Finally, the model was able to maintain its high performances (AUC: 0.982, 94.4% sensitivity at 95% specificity) even when sequencing depth was down-sampled to 1X coverage.

“A non-invasive liquid-biopsy based assay can be used to screen high-risk population, which would greatly facilitate the diagnosis of advCRA or CRC at an early stage”, says Dr. Xue Wu, author and the Dean of Geneseeq Research Institute. After years of research and development, the research team from Geneseeq investigated various liquid biopsy-based early screening technologies such as cfDNA mutation, methylation, fragmentomics characteristics, metagenomics, and finally developed an early screening technology, MERCURY. Through collaborations with clinicians, Geneseeq has carried out a series of early screening studies DECIPHER in common solid tumor types. The preliminary data of the DECIPHER-Lung, DECIPHER-Liver and DECIPHER-Colon studies have been released at the WCLC and EMSO conferences in 2021, showing excellent early screening performance.