microRNA-944 overexpression is a biomarker for poor prognosis of advanced cervical cancer.

BACKGROUND: One-third of cervical cancer patients are still diagnosed at advanced stages. The five-year survival rate is decreased in about 50% of advanced stage cervical cancer patients worldwide, and the clinical outcomes are remarkably varied and difficult to predict. One of the miRNAs known to be associated with cancer tumorigenesis is miR-944. However, the prognostic value of miR-944 in cervical cancer has not been fully investigated. The aim of this study was to analyze clinical significance and prognostic value of miR-944 in cervical cancer. METHODS: The expression levels of miR-944 were detected using quantitative reverse transcription polymerase chain reaction in five types of cervical cancer cell lines and 116 formalin-fixed paraffin-embedded (FFPE) cervical tissues. The association between the expression levels of miR-944 and prognostic value was analyzed using the Kaplan-Meier analysis and Cox proportional hazards model. RESULTS: The expression levels of miR-944 in cervical cancer tissues were significantly higher compared with those in normal tissues (P < 0.0001). Moreover, the expression levels of miR-944 in cervical cancer cell lines and FFPE tissues with human papillomavirus (HPV) infection were significantly higher compared to those without HPV infection (P < 0.01 and P = 0.02). High miR-944 expression was also markedly associated with bulky tumor size (P = 0.026), advanced International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.042), and lymph node metastasis (P = 0.030). In particular, high miR-944 expression group showed shorter overall survival than the low miR-944 expression group in the advanced FIGO stage (84.4% vs. 44.4%, HR = 4.0, and P = 0.01). CONCLUSIONS: These results suggest that miR-944 may be used as a novel biomarker for improving prognosis and as a potential therapeutic target.

MiR-9, miR-21, and miR-155 as potential biomarkers for HPV positive and negative cervical cancer.

BACKGROUND: Cervical cancer is the second leading cause of death among female patients with cancer in the world. High risk human papillomavirus has causal roles in cervical cancer initiation and progression by deregulating several cellular processes. However, HPV infection is not sufficient for cervical carcinoma development. Therefore, other genetic and epigenetic factors may be involved in this complex disease, and the identification of which may lead to better diagnosis and treatment. Our aim was to analyze the expression of microRNAs in cervical cancer cases positive or negative for HPV E6/E7 mRNA, and to assess their diagnostic usefulness and relevance. METHODS: The expression of three different microRNAs (miR-9, miR-21, and miR-155) in 52 formalin-fixed paraffin-embedded (FFPE) primary cervical cancer tissue samples and 50 FFPE normal cervical tissue samples were evaluated. RESULTS: MiR-9, miR-21, and miR-155 were significantly overexpressed in cervical cancer tissues compared to normal tissues (P < 0.001). MiR-21 and miR-155 expression combined with the HPV E6/E7 mRNA assay in HPV E6/E7 negative cervical cancer showed increased AUC of 0.7267 and 0.7000, respectively (P = 0.01, P = 0.04), demonstrating their potential as diagnostic tools. Moreover, miR-21 and miR-155 were predictors showing a 7 fold and 10.3 fold higher risk for HPV E6/E7 negative patients with cervical cancer (P = 0.024 and P = 0.017, respectively) while miR-155 was a predictor showing a 27.9 fold higher risk for HPV E6/E7 positive patients with cervical cancer (P < 0.0001). CONCLUSIONS: There is a strong demand for additional, alternative molecular biomarkers for diagnosis and management of precancer patients. MiR-21 and miR-155 may be helpful in the prediction of both HPV positive and HPV negative cases of cervical cancer.