PS02.237: IDENTIFICATION OF THREE DISTINCT BIOLOGICAL SUBTYPES IN ESOPHAGEAL AND JUNCTIONAL ADENOCARCINOMA BY RNA SEQUENCING. (14th September 2018)

• Record Type: Journal Article
• Authors: Krishnadath, Kausilia; Hoefnagel, Sanne; Calpe, Silvia; Sancho-Del Serra, Carmen; Van Berge Henegouwen, M I; Hulshof, Maarten; Van Laarhoven, Hanneke; Gisbertz, Suzanne; Bergman, Jacques; Koster, Jan
• Is Part Of: Diseases of the esophagus. Volume 31(2018)Supplement 1
• Page Start: 189
• Page End: 189
• Publication Date: 2018-09-14
• Subjects: Esophagus -- Diseases -- Periodicals; 616.32
• DOI: 10.1093/dote/doy089.PS02.237
• Languages: English
• ISSNs: 1120-8694

Abstract

Abstract: Background: Advances in therapy have achieved incremental improvements in overall outcome in patients with Esophageal Adenocarcinoma (EAC), but over- and undertreatment of undefined subgroups of patients might undermine these benefits. The biological diversity of EAC complicates patient selection and treatment stratification and impedes the development of new targeted agents. Further insight into the heterogeneous molecular pathology of EAC to select patients for standard chemo-radiotherapy and/or novel targeted strategies is urgent. Methods: In our analysis, we included 110 patients with EAC and junctional adenocarcinomas diagnosed between 2012 and 2017. Patients either received neoadjuvant chemo-radiotherapy (nCRT) with carboplatin and paclitaxel, followed by surgical resection or chemotherapy only. Pre-treatment tissue samples of the tumor were collected during upper gastrointestinal endoscopy. RNA was extracted from these samples and RNA sequencing profiles were obtained. We performed unsupervised hierarchical clustering on the tumor RNA profiles to identify distinct subtypes. We used a machine learning approach to train a model with our AMC dataset. This model was applied to the a public TCGA dataset. Results: We could identify three distinct biological subtypes. We found that that subgroup 2 and 3 had slightly poorer overall survival, although the difference was not significant. The TCGA dataset resulted in the identification of similar groups with similar signatures. One of the pathways that we discovered proved to be highly upregulated in group 2, was NOTCH signaling. Genes within the NOTCH signaling pathway can be targeted by specific antibodies that are currently in research phase for several types of cancer. Conclusion: Our studies support the existence of three distinct EAC/junctional subtypes. Clinical use of an EAC subtype classifier might lead to identification of new therapeutic targets and improve stratification of patients for (targeted) therapies and subsequently improve outcomes. However, our results need to be further validated in independent cohorts. Disclosure: All authors have declared no conflicts of interest.