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Blood plasma mRNA sequencing for monitoring therapy response in esophageal adenocarcinoma patients
Background
The incidence of esophageal adenocarcinoma (EAC), a histological subtype of esophageal cancer, has rapidly increased in the Western world in the last decades. It is an aggressive cancer with an unacceptably low five-year survival rate (10–25%), despite improved treatment strategies. The tumor is often detected in a late stage due to a lack of symptoms or they are not recognized. This results in a complex treatment and tough recovery. Neoadjuvant chemoradiotherapy is ineffective for many patients. These patients will be in a weakened condition prior to this complex surgery, resulting in a potentially longer and more difficult recovery afterwards. Current diagnostics do not allow prediction of which patients will benefit from this pre-treatment. Being able to do so would allow the clinicians to develop an improved and patient-specific treatment plan. A blood-based test is attractive for this purpose, because it is easy to obtain and provides almost no discomfort to the patient. The aim of this study is to identify circulating RNA biomarkers in patients with esophageal adenocarcinoma to monitor treatment response.
Methods
In this study 13 patients with EAC were included, with plasma sample collections before treatment and at least one sample after chemoradiotherapy and/or after surgery. Most patients received neoadjuvant chemoradiotherapy, with treatment response scores (Mandard scores determined by pathologists) ranging from 1-5. RNA extraction and subsequent mRNA capture sequencing was done on all patient plasma samples. Quality checks were done prior to data analysis.
Results
Differential gene abundance shows approximately 600 significantly up- or downregulated genes comparing plasma before and after neoadjuvant therapy and surgical resection. Most differentially abundant genes are observed comparing before and after surgery. Enrichment analysis shows that several of these significantly abundant genes are targets of MYC. From the gene expression data it can be observed that the abundance of all these genes decreases over time during treatment. Interestingly, for two patients with relapse/metastasis at later time points, the abundance of these genes is increasing again.
Conclusions
Preliminary data from this project shows that MYC targets are significantly downregulated after neoadjuvant chemoradiotherapy and continue to decrease after surgical removal of the tumor. These encouraging results require further validation to assess the potential to distinguish responders and non-responders to neoadjuvant therapy.
Legal entity responsible for the study
The authors.
Funding
Ghent University Special Research Fund (BOF) and Concerted Research Action (BOF-GOA), and Kom Op Tegen Kanker (Stand up to Cancer).
Disclosures
All authors have declared no conflicts of interest.
