Abstract
ObjectiveAccumulating evidence for differential expression of microRNA-224 (miR-224) in various types of human cancer suggests that it may be play a crucial role in tumor biology. The previous microarray detection also shown that miR-224 was one of miRNAs with significant upregulation in cervical cancer tissues relative to adjacent normal tissues. However, little is known about the function of miR-224 in human cervical cancer. The aim of this study was to investigate the clinical significance of miR-224 expression in cervical cancer.MethodsMiR-224 expression in 126 pairs of fresh human cervical cancer and adjacent normal tissues was measured by real-time quantitative RT-PCR assay.ResultsmiR-224 expression was significantly upregulated in cervical cancer tissues when compared with corresponding adjacent normal tissues (P < 0.001). It was also significantly higher in the cancerous tissues of patients with advanced FIGO stage cervical cancer than those with early FIGO stage (P = 0.02). In addition, miR-224 was expressed at significantly higher levels in lymph node metastasis-positive patients than in lymph node metastasis-negative patients (P = 0.008). Moreover, we found that lesser differentiated tumors expressed higher miR-224 (P = 0.03). Finally, there were sufficient evidence to confirm its value in the status of vascular invasion (P = 0.01) and human papillomavirus (HPV) infection (P = 0.02) in cervical cancer. More importantly, Kaplan-Meier analysis showed that cervical cancer patients with high miR-224 expression tend to have shorter overall survival. In multivariate analysis stratified for known prognostic variables, miR-224 was identified as an independent prognostic marker.ConclusionOur data indicated that miR-224 upregulation was associated with aggressive progression and poor prognosis in cervical cancer. MiR-224 was identified for the first time as an independent marker for predicting the clinical outcome of cervical cancer patients.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2170449349527493
Highlights
Cervical cancer is the third most common malignancy among women worldwide, with an estimated global incidence of over 500,000 new cases and tremendously high death cases of 260,000 annually [1]
There were sufficient evidence to confirm its value in the status of vascular invasion (P = 0.01) and human papillomavirus (HPV) infection (P = 0.02) in cervical cancer
Our data indicated that miR-224 upregulation was associated with aggressive progression and poor prognosis in cervical cancer
Summary
Cervical cancer is the third most common malignancy among women worldwide, with an estimated global incidence of over 500,000 new cases and tremendously high death cases of 260,000 annually [1]. Aberrant expression levels of miRNAs have been demonstrated to be involved in several forms of solid tumors such as hepatocellular carcinoma, colorectal cancer, prostate cancer, cervical cancer, breast cancer, ovarian carcinoma, and lung cancer [7,8,9,10]. They function either as tumor suppressors or oncogenes according to the roles of their target genes. Xu et al [13] identified a crucial tumor suppressive role of miR-424 in the progression of cervical cancer at least partly via upregulating the expression of Chk and p-Chk, suggesting that miR-424 may be a candidate of prognostic predictor or an anticancer therapeutic target for cervical cancer patients
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