RESUMO
Cervical cancer screening is based on cytologic analysis and high-risk human papillomavirus (HR-HPV) testing, each having their drawbacks. Implementation of new biomarker-based methods may improve screening accuracy. Here, the levels of 25 microRNAs (miRNAs, miRs) and 12 mRNAs involved in cervical carcinogenesis in 327 air-dried Papanicolaou-stained cervical smears from patients with cervical precancerous lesions, cancer, or without the disease were estimated by real-time PCR. Using logistic regression analysis, small-scale miRNA-based, mRNA-based, and combined molecular classifiers were built based on paired ratios of miRNA or mRNA concentrations; their ability to detect high-grade cervical lesions and cancer was then compared. Combined mRNA-miRNA classifiers manifested a better combination of sensitivity and specificity than miRNA- and mRNA-based classifiers. The best classifier, combining miR-375, miR-20, miR-96, CDKN2A, TSP4, and ECM1, predicted high-grade lesions with diagnostic sensitivity of 89.0%, specificity of 84.2%, and a receiver-operating characteristic area under the curve of 0.913. Additionally, in a subsample of the same specimens, the levels of MIR124-2 and MAL promoter methylation, HR-HPV genotypes, and viral loads were analyzed. The relative high-grade lesion risk estimated by the classifier correlated with the frequency of MAL and MIR124-2 methylation but not with the HR-HPV genotype or viral load. The results support the feasibility of cellular biomarker-based methods for cervical screening and patient management.
Assuntos
Biomarcadores Tumorais/genética , Detecção Precoce de Câncer/métodos , MicroRNAs/genética , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , RNA Mensageiro/genética , Neoplasias do Colo do Útero/diagnóstico , Adulto , Citodiagnóstico , DNA Viral/genética , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/virologia , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/virologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/genética , Displasia do Colo do Útero/virologiaRESUMO
Endometriosis is a chronic disease characterized by the growth of endometrial tissue outside of the uterine cavity. Endometriosis affects up to 10% of women of reproductive age and has great social impact. The diagnostics of endometriosis are based on clinical appearance, ultrasound, and magnetic resonance imaging (MRI); however, a diagnosis is frequently hampered by the absence of objective criteria. Adenomyosis (AM) is a particular type of endometriosis wherein the spread of the ectopic endometrial gland is limited by the uterine myometrium. Alteration of the microRNA expression profile in the eutopic endometrium can be associated with AM, and may be assayed for diagnostic purposes. In the presented study, we aimed to explore the diagnostic potency of this approach. Eutopic endometrium specimens were collected from patients (n = 33) and healthy women (n = 30). The microRNA expression was profiled to select individual microRNAs with AM-associated expression alterations. A new method of two-tailed RT-qPCR microRNA analysis was applied to assay potential markers. The expression ratios of reciprocally dysregulated microRNAs were calculated, and the diagnostic potency of these parameters was evaluated by receiver operation curve (ROC) analysis. Mir-10b, miR-200c and miR-191 were significantly dysregulated in the eutopic endometrium of AM patients. The expression ratio of reciprocally dysregulated microRNAs allowed us to diagnose AM with a range of sensitivity from 65% to 74%, and of specificity from 72% to 86%. The analysis of microRNAs from the eutopic endometrium might present a promising low-invasive method of AM diagnostics.