miR-99a-5p as Possible Diagnostic and Prognostic Marker in Patients With Gastric Cancer

BACKGROUND: The signet-ring cell carcinoma (SRC), one of the histological subtypes of gastric cancer, often exhibits aggressive behavior in clinical practice and is therefore a commonly found subtype in advanced gastric cancer. However, SRC, especially at the early stages, has recently been reported to show a lower potential for malignancy than other pathological subtypes. Because the detailed molecular mechanisms underlying SRC pathology remain unclear, we focused on microRNAs (miRs) and aimed to elucidate the molecular mechanisms involved in endowing early SRC with its characteristic properties. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded samples of patients diagnosed with various pathological subtypes of gastric cancer including SRC were used to purify and subsequently evaluate miRs. RESULTS: As expected, patients with SRC were observed to have significantly high miR-99a-5p expression. Further, high miR-99a-5p expression was found to closely correlate with less aggressive clinicopathological features, and functional studies probed by overexpression of miR-99a-5p resulted in inhibition of proliferation in two SRC cell lines. CONCLUSIONS: The present study reports that high levels of miR-99a-5p were observed in patients with SRC, particularly those with early stage SRC. In addition, miR-99a-5p expression was found to be related to cell proliferation. Therefore, miR-99a-5p could emerge as a diagnostic biomarker for early SRC and lymph node metastases or related adverse prognosis in patients.