Cornelia Braicu

Identification of Core Genes Involved in the Progression of Cervical Cancer Using an Integrative mRNA Analysis

In spite of being a preventable disease, cervical cancer (CC) remains at high incidence, and it has a significant mortality rate. Although hijacking of the host cellular pathway is fundamental for developing a better understanding of the human papillomavirus (HPV) pathogenesis, a major obstacle is identifying the central molecular targets involved in HPV-driven CC. The aim of this study is to investigate transcriptomic patterns of HPV-infected and normal tissues to identify novel prognostic markers. Analyses of functional enrichment and interaction networks reveal that altered genes are mainly involved in cell cycle, DNA damage, and regulated cell-to-cell signaling. Analysis of The Cancer Genome Atlas (TCGA) data has suggested that patients with unfavorable prognostics are more likely to have DNA repair defects attributed, in most cases, to the presence of HPV. However, further studies are needed to fully unravel the molecular mechanisms of such genes involved in CC.

Alteration of Gene and miRNA Expression in Cervical Intraepithelial Neoplasia and Cervical Cancer

Background: Cervical cancer is one of the most common malignancies in women in terms of prevalence and mortality. Cervical cancer has some particularities that distinguish it from any other oncologic pathology: first, it is completely preventable by prompt detection of its precursor, cervical intraepithelial neoplasia (CIN); second, the Human Papillomavirus (HPV) infection is a known etiological agent; third, the mean age at diagnosis is much lower than in other oncologic conditions, as a consequence of the sexually-transmitted HPV. Methods: We evaluated the expression level of several long noncoding RNAs and a microRNA in samples from 30 patients with CIN, 9 with cervical cancer and 38 normal samples using qRT-PCR technology. Results: We observed higher expression levels for MEG3, DAPK1, MLH1 and MALAT1 in CIN samples than in normal samples, whereas TIMP3 and SOX1 had lower expression levels. For cancer samples, DAPK1, MLH1 and MALAT1 had higher expression, and MEG3, TIMP3 and SOX1 had lower expression when compared to normal samples. In the case of CIN versus cancer samples, only MEG3 gene showed a statistically significant difference. The expression of miR-205-5p was lower in both CIN and cancer samples compared to normal samples. Conclusion: Decreased MEG3 expression could be considered an alarm signal in the transition from a premalignant cervical lesion to invasive cancer, while altered expression levels of TIMP3, SOX1, MLH1, MALAT1 and miR-205-5p could serve as early biomarkers in the diagnosis of premalignant cervical lesions. Future studies, including a larger number of patients with CIN, will be of particular importance in validating these observations.