Validation study of a high-performance whole-blood assay for the detection of colorectal advanced adenomas in average risk population

The benefits of CRC screening are limited by low compliance of colonoscopy and stool-based screening methods, resulting in one in three eligible adults not up to date with screening 1 . Moreover, projections for 2040 estimate a 60% increase in CRC incidence rate, highlighting an urgent need for prevention and novel screening strategies 2 . An accurate non-invasive blood-based test that can effectively screen for benign neoplastic colorectal lesions is key to promote prevention and reduce mortality 3 . Previously we have presented discovery data on a next generation whole-blood test with high reliability and best-in-class performance for Advanced Adenoma (AA) detection 4 . In the current study we present validation data on an independent European cohort.

A discovery set of 160 European colonoscopy-screened subjects (98 Negative by Colonoscopy (NC) and 62 AA, including sessile serrated lesions > 10mm) was used to develop a gene expression signature for AA detection. Full transcriptome profiles were generated by RNA-seq from peripheral whole blood, and a gene signature was identified using Novigenix LITOseek® platform, feature selection pipeline and predictive machine learning algorithms. The predictive accuracy of the gene signature was determined using an independent set of 179 subjects at average risk for CRC and enrolled in screening settings in the EU (75 NC, 26 AA of which 77% with no or low-grade dysplasia, and 78 non-advanced adenoma (NAA)).

The predictive accuracy of the whole-blood assay on the independent EU cohort demonstrated a 42.3% sensitivity at 90.5% specificity for detection of AA against those that were negative by colonoscopy (AUC of 0.78). Importantly, sensitivity was high for AA located in the proximal colon (53%). The positivity rate on NAA subjects was only 15%. Further analysis is ongoing to evaluate performance on additional European and US subjects diagnosed with AA and NC.

A new generation whole-blood transcriptome test has been developed for the detection of AA, and results from this validation study demonstrate a high detection rate for precancerous lesions, including in the proximal colon. Combined with improved adherence rates with blood-based CRC screening tests as compared to other screening methods, this blood-based technology may lead to improved prevention strategies for colorectal cancer.

The authors.

Has not received any funding.

S. Hosseinian: Leadership role: Novigenix SA, Novigenix SA, Novigenix SA; Shareholder / Stockholder / Stock options: Novigenix SA, Novigenix SA, Novigenix SA; Full / Part-time employment: Novigenix SA, Novigenix SA, Novigenix SA; Officer / Board of Directors: Novigenix SA, Novigenix SA, Novigenix SA. V. Wosika: Full / Part-time employment: Novigenix SA. S. Monnier-Benoit: Full / Part-time employment: Novigenix SA. L. Ciarloni: Shareholder / Stockholder / Stock options: Novigenix SA; Full / Part-time employment: Novigenix SA. B. Hashemi: Leadership role: Novigenix SA, Novigenix SA, Novigenix SA; Shareholder / Stockholder / Stock options: Novigenix SA; Officer / Board of Directors: Novigenix SA. P. Romero: Full / Part-time employment: Novigenix SA. S. Tejpar: Advisory / Consultancy: Novigenix SA. The author has declared no conflicts of interest.