Abstract
BackgroundCervical 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.MethodsThe 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.ResultsMiR-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).ConclusionsThere 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.
Highlights
Cervical cancer is the second leading cause of death among female patients with cancer in the world
We found that all 50 formalin-fixed paraffin-embedded (FFPE) normal cervical control samples were negative for HPV E6/E7 mRNA expression (Table 1)
The area under the Receiver operating characteristic (ROC) curve (AUC) was 0.7565 [95% confidence interval (CI) = 0.6624–0.8507] in miR-9, 0.8325 in miR-21, and 0.8492 in miR-155, all of which indicate these miRNAs may be used as potential biomarkers for cervical cancer (Fig. 1d-f )
Summary
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. 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. High risk human papillomavirus (HR-HPV) infection is recognized as the most important risk factor in cervical cancer. Persistent over-expression of Recently, several studies reported the development of cervical cancers that are HPV negative despite increased sensitivity of HR-HPV detection methods. A large international retrospective cross-sectional study including 10,575 cases with invasive cervical cancer found that 15% (1598 cases) were negative for HPV DNA [9]. Our previous study found that 15% of patients with cervical cancer (100 cases) were HPV negative [10]
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