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Chapter 598completely known. Upregulation of miR-375 increased the cisplatin-sensitivity of gastric cancer cells[46]. In our study, no significant relation was found between circulating miR-200c3p, miR-21-5p or miR-148a-3p expression and OS or PFS in patients with EAC. Upregulated miR-21 in tissue of patients with EAC was previously associated with a worse prognosis[25] and resistance to gemcitabine treatment in other tumor types[26]. Upregulated miR-148 in tissue was also suggested to be associated with a worse prognosis in EAC[10]. In our study, no significant relation was found between circulating miR-375, miR-200c-3p, miR-21-5p or miR-148a-3p expression and survival in patients with ESCC. miR-200c, miR-148 and miR-375 were previously suggested to function as a tumour suppressor gene in ESCC [15,23]. A high baseline expression of miR-200c-3p showed a trend towards a worse OS of patients with GC in our study. Similar results were reported in earlier studies evaluating the function of miR-200c in GC, although it has been shown that a high miR-200c expression may activate the AKT pathway, leading to resistance to cisplatin[47]. High miR-200c levels in the blood of patients with GC were previously also associated with poor OS [13,15]. Interestingly Li et al. reported an association of higher miR-200c levels with better survival outcomes [16]. No significant relation between miR-141-3p, miR-146a-5p or miR-218-5p expression and survival in patients with GC were found in our study. Previous reports suggest that miR-141 and miR-146a may function as a tumour suppressor gene in GC [18,20,31]. miR-218 expression was found to be higher in GC cells sensitive for fluorouracil, oxaliplatin or adriamycine [48].The difference in results between our study and the previously reported results could be related to the fact that only a few of the available studies focused on patients that were treated with platinum containing chemotherapy for advanced EC and GC. The studies that reported miRNA measurements during chemotherapy were performed in Asian populations and focused on miR-200c3p[16,23,24]. Unless optimisation of the heparinase treatment we cannot exclude an effect of the relatively old heparinized plasma samples that were used for analysis of miRNA samples in this study. Twenty of the 38 included patients received supplementation with vitamin B12 and folic acid in addition to cisplatin and gemcitabine. We previously reported that the addition of folic acid and vitamin B12 did not improve RR, PFS or OS [28]. A folate deficient environment is associated with in vitro alteration of various