Novel genomic classifier for early stage colorectal cancer patients

Abstract

Background: Identifying patients at risk of relapse in early colorectal cancer (CRC) stages is an unmet clinical need. Due to the limitations of clinicopathological variables in predicting individual risk of recurrence in CRC patients, genomic information has increasingly gained prominence as a potential method for patient stratification. We have previously shown that Myosin Vb (MYO5B) expression alone or in combination with the expression of its adapter protein RAB8A shows strong prognostic value in early CRC patients (PMID 29024942). Methods: We are currently setting up a meta-analysis including multiple CRC datasets, which allows to further validate the prognostic value of the genomic classifier. Additionally, this meta-analysis will determine the predictive value of the classifier on chemotherapy efficiency. Furthermore, pre-analytical and analytical assays will assess the reproducibility, sensitivity and specificity of the biomarker. Finally, we will prospectively collect stage II CRC tumor samples to clinically validate our classifier. Results: In the follow-up study, we have now validated the prognostic value of the classifier in independent datasets. By multivariate analysis, we show that the gene expression signature is independent of clinicopathological features currently used in the clinics (stage, grading, T3, MSI status among others). Importantly, the identified molecular classifier outperformed the other three molecular tests (Oncotype DX, Coloprint and Oncodefender) that are commercially available but not FDA approved for predicting patient relapse. We will report on the predictive value of our molecular classifier on chemotherapy efficiency. In addition, first results on the pre-analytical and analytical analysis of the classifier will be presented. Conclusions: Altogether, MYO5B together with RAB8A might allow delineating a high-risk population in early CRC stages. This stratification could potentially help oncologists to choose the best treatment plan, especially for stage II patients, where adjuvant chemotherapy may not always lead to beneficial results, but still results in significant side-effects.