A case series and a systematic review of the literature on upregulated miRs in gastric cancer: a story still to be told.

Background: Recent literature documented the expression of miRs in gastric cancer (GC), however their clinical utility is still unclear. Methods and Results: 117 resected GCs were evaluated for miR21, miR135b, miR196a, miR196b relative expression (RE). The performance of miRs’ to differentiate cancer vs normal mucosa was tested using ROC curves. Univariable and multivariable analyses were conducted to correlate miRs RE with pathological features and survivals. Although all the 4 miRs were upregulated, ROC curves documented that this was not-significant in differentiating GC (p ns). miR135b significantly correlated with Lauren’s intestinal type and more advanced pT stages (p 0.017, and p 0.025), whereas miR196a and miR196b were more expressed in advanced pStages (p 0.016, and p 0.038). miR196b was also more expressed in nodal positive patients comparing N0 (p 0.035). Survival curves were non-significant for miRs RE, while pStages could significantly differentiate oncological outcomes (p<0.0001). On Cox analyses, pStages independently correlated with OS (HR 4.9, 95%CI 2.041-12.104), whereas increased age correlated with a worse DFS (HR 6.0, 95%CI 2.596-13.947), and lymph-node ratio with DSS (HR 14.4, 95%CI 4.213-49.373). Literature was reviewed a using PRISMA method focusing on miRs and response to therapy and the detection of peritoneal metastases: out of 116 manuscripts retrieved, just 41 were pertinent with the outcomes of interest, and 14.6% were from Western countries. miR21, miR135b and miR204 were reported to correlate with response to therapy. Conclusions: miR21, miR135b, miR196a and miR196b were documented up-regulated in GC, but their clinical utility is still to be fully investigated.