Increased expression of miR-222 is associated with poor prognosis in bladder cancer

BACKGROUND MicroRNA-222 (miR-222) has been shown to play a potential oncogenic role in bladder cancer. The aim of this study was to evaluate the expression of miR-222 in bladder cancer and its potential relevance to clinicopathological characteristics and patient survival. METHODS Surgical specimens of cancer tissue and adjacent normal tissue were obtained from 97 patients with bladder cancer. The relative expression levels of miR-222 in the cancer and the normal adjacent tissue were measured by quantitative reverse-transcriptase PCR. We analyzed their correlation with clinicopathological parameters and prognostic value. RESULTS The expression level of miR-222 was significantly higher in tumor tissues than in corresponding non-cancerous tissues (5.46 ± 1.45 versus 1.92 ± 0.65, P <  0.0001), and a high expression of miR-222 was found to be significantly associated with tumor grade (P = 0.003) and tumor stage (P = 0.005). The miR-222 expression level was classified as high or low in relation to the median value (cutoff value = 5.15). Kaplan-Meier analysis showed that patients with higher levels of miR-222 had significantly poorer survival than those with lower expression of this miRNA in patients, with a 5-year overall survival of 29.53% and 52.75%, respectively (P = 0.0034). In the multivariate Cox proportional hazards analysis, which included miR-222 level, tumor grade, tumor stage, and tumor number, high miR-222 expression was independently associated with poor survival (P < 0.001; hazard ratio 6.17; 95% CI 2.33 to 10.39). CONCLUSION miR-222 overexpression is involved in the poor prognosis of bladder cancer and can be used as a biomarker for selection of cases requiring special attention.