Page 89 - Demo

Plasma microRNAs in oesophageal and gastric cancer875IntroductionEsophagogastric cancer is one of the most common malignancies of the gastrointestinal tract worldwide. The most common histologic subtypes of this disease are adenocarcinomas (AC) and squamous cell carcinomas (SCC)[1]. The incidence of oesophageal adenocarcinoma (EAC) (predominantly in the distal oesophageal and esophagogastric junction) has increased in Western countries and accounts for > 60 percent of all oesophageal cancers (EC) in the United States [2]. Treatment for metastatic disease frequently consists of palliative chemotherapy and/or radiotherapy[3]. The median overall survival (OS) after palliative chemotherapy is around 11 months [4,5]. Though, response and survival rates vary among patients. Prognostic and predictive biomarkers have been proven beneficial for treatment selection. For example, a survival benefit has been observed for anti-HER2 directed therapies in patients with HER2-neu overexpressing gastro-oesophageal junction tumours [6].MicroRNAs (miRNAs) are a class of small (approximately 22 nucleotides in length) non-coding RNAs that mediate gene expression through complementary binding to the 3'untranslated regions (3%u2019UTRs) of target messenger RNA (mRNA) genes [7]. miRNAs that target tumour suppressor genes function as oncogenes while miRNAs that target oncogenes exert a tumour suppressor function[8] in different cancer types[9]. Tumour or plasma specific miRNA signatures of patients with EC and gastric cancer (GC) were previously associated with clinical outcome [10-27]. The definite role of miRNAs in EC and GC is unclear due to conflicting study outcomes, [13,15,16] and limited data are available about the function of miRNAs in plasma of patients treated with palliative chemotherapy. In order to investigate the prognostic and predictive value of ci-miRNAs in patients treated with palliative gemcitabine-cisplatin based chemotherapy for advanced EC and GC, the expression levels of miR-200c-3p, miR-375, miR-21-5p, miR-148a-3p, miR146a-5p, miR-141-3p and miR-218-5p, which were selected based on literature, were quantified with droplet digital PCR (ddPCR) in plasma samples collected during a randomized phase II clinical trial.