OGC P22 The Use of miRNAs in Predicting Response to Neoadjuvant Therapy in Oesophageal Cancer

Abstract

Abstract Background Oesophageal cancer (OC) is the ninth most common cancer worldwide. Patients receive neoadjuvant therapy (NAT) as standard of care, but less than 20% of patients with oesophageal adenocarcinoma (OAC) or a third of oesophageal squamous cell carcinoma (OSCC) patients, obtain a clinically meaningful response. Being able to predict which patients will respond to chemotherapy and chemoradiotherapy before they receive this treatment will prevent patients undergoing unnecessary procedures that may reduce their quality of life and help source alternative treatment options faster. This will allow rational treatment decisions to be made, thus improving patient outcome and quality of life. Epigenetic mechanisms involving microRNAs that regulate gene expression during cancer have been implicated as a viable non-invasive potential solution to improving the accuracy of patient allocation to treatment. The expression levels of microRNAs within the body can change throughout the course of neoadjuvant therapy. In this study, we aim to determine the use and accuracy of microRNAs as biomarkers of response to NAT in patients with OAC or OSCC. Methods A systematic review was conducted. Using the PICO framework focused research questions and inclusion and exclusion criteria were developed. Online databases MEDLINE, EMBASE, Web of Science and the Cochrane library were searched to identify studies conducted from January 1st 1990 onward. The included studies investigated the expression of microRNAs taken before treatments to predict response to neoadjuvant therapy in patients with OAC and OSCC. Studies analysing OAC, OSCC or both together were considered separately. Quality and risk of bias was assessed using the Quality in Prognostic Studies (QUIPS) assessment tool. Results 11,656 articles were identified, out of which 63 articles met the inclusion criteria and 15 were deemed eligible after full-text review. Across the 15 studies included in this systematic review, a panel of 20 microRNAs were identified as predictors of good or poor response to NAT. Specifically, miR-99b, miR-451 and miR-505 showed the strongest ability to predict response to NAT in OAC patients along with miR-193b in OSCC patients. This review has provided evidence suggesting that microRNAs may be robust biomarkers for predicting response to NAT by differentiating between responders and non-responders. However, the utilization of singular microRNAs to predict response to NAT is unlikely to be as sensitive or specific as looking at the microRNA expression profiles of multiple microRNAs. Conclusions The ability to predict OC in patients that will respond to NAT is vital to improve clinical outcomes whilst reducing treatment associated morbidity. MicroRNAs are valuable biomarkers of response to NAT in patients with OC. However, more research is needed to understand the effects different types of chemotherapy and chemoradiotherapy have on the predictive value of microRNAs; studies also require greater standardisation in how response is defined. Finally, validation studies are required to see the translation of such biomarkers in clinical practise.