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Background  The goal of this study is to evaluate the effectiveness of S-1/Oxaliplatin vs. Doxifluridine/Oxaliplatin regimen and to identify miRNAs as potential prognostic biomarkers in gastric cancer patients. The expression of candidate miRNAs was quantified from fifty-five late stage gastric cancer FFPE specimens.    Experimental Design  Gastric cancer patients with KPS>70 were recruited for the trial. The control group was treated with 400 mg/twice/day Doxifluridine plus  i.v.  with Oxaliplatin at 130 mg/m 2 /first day/4 week cycle. The testing group was treated with S-1 at 40 mg/twice/day/4 week cycle plus  i.v.  with Oxaliplatin at 130 mg/m 2 /first day/4 week cycle. Total RNAs were extracted from normal and gastric tumor specimens. The levels of miRNAs were quantified using real time qRT-PCR expression analysis.    Results  The overall objective response rate (CR+PR) of patients treated with S-1/Oxaliplatin was 33.3% (CR+PR)  vs.  17.6% (CR+PR) with Doxifluridine/Oxaliplatin for advanced stage gastric cancer patients. The average overall survival for patients treated with S-1/Oxaliplatin was 7.80 month vs. 7.30 month with patients treated with Doxifluridine/Oxaliplatin. The expression of miR-181b ( P  = 0.022) and miR-21 ( P  = 0.0029) was significantly overexpressed in gastric tumors compared to normal gastric tissues. Kaplan-Meier survival analysis revealed that low levels of miR-21 expression (Log rank test, hazard ratio: 0.17, CI = 0.06–0.45;  P  = 0.0004) and miR-181b (Log rank test, hazard ratio: 0.37, CI = 0.16–0.87;  P  = 0.018) are closely associated with better patient's overall survival for both S-1 and Doxifluridine based regimens.    Conclusion  Patients treated with S-1/Oxaliplatin had a better response than those treated with Doxifluridine/Oxaliplatin. miR-21 and miR-181b hold great potential as prognostic biomarkers in late stage gastric cancer.

Prognostic Significance of miR-181b and miR-21 in Gastric Cancer Patients Treated with S-1/Oxaliplatin or Doxifluridine/Oxaliplatin