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.
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. Electronic supplementary material The online version of this article (10.1186/s12885-019-5620-6) contains supplementary material, which is available to authorized users.
Objectives: Human papillomavirus (HPV) is a major cause of cervical cancer, which is the second most common cancer in women. HPV E6 initiates degradation of cellular tumor suppressor protein p53, induces human telomerase reverse transcriptase (hTERT) activity, and then leads to progressive cervical carcinogenesis. Methods:Results: The positivity for the HPV E6/E7 messenger RNA (mRNA) assay was 94. 4%, 95.2%, 82.4%, 46.5%, 25.0%, and 1.1% in squamous cell carcinomas,, atypical squamous cellscannot exclude HSIL, low-grade squamous intraepithelial lesions, atypical squamous cells of undetermined significance, and normal cytology samples, respectively. Five cervical intraepithelial neoplasia grade 2+ samples were not detected by the HPV E6/E7 mRNA assay, but they exhibited positive signals in the hTERT mRNA assay. Notably, the hTERT mRNA expression level was increased in high-grade cervical lesions but was very low in all 288 normal samples. Conclusions:These data suggest that the combination of HPV E6/E7 and hTERT mRNA expression levels could be used in a complementary manner in diagnosing high-grade cervical lesions and malignant tumors and might be useful as a predictive marker in monitoring low-grade cervical lesions.Cervical cancer, which develops from cervical intraepithelial neoplasia (CIN), is the second most common malignancy in women worldwide and is a major cause of morbidity and mortality. 1 While the overall incidence of cervical cancer is declining, 493,000 new cases and 274,000 deaths occur each year. 2 Human papillomavirus (HPV) is the most common sexually transmitted pathogen among women and men, and it has been estimated that 70% of sexually active women will acquire an HPV infection at some point during their lifetime. HPVs are small double-stranded DNA viruses that infect basal cells and replicate within the nucleus of squamous epithelial cells. 3 Cervical cancer is caused by persistent infection with oncogenic HPV genotypes that belong to a few phylogenetically related high-risk (HR) species. Some HPV genotypes are able to infect cutaneous tissues, resulting in the formation of warts on the hands or feet, while others infect the oral mucosa. HPV genotypes that infect the genital epithelia are well characterized and can be grouped as HR species because of their association with cervical cancer. As a result, testing for oncogenic HPV infection in cervical lesions could serve as an accurate means of identifying women who are at risk for developing cervical cancer. HR HPV genotypes, including 16, 18, 33, 45, 52, 58, 39, 51, 56, and 59, are detected in more than 90% of cervical cancer cases. 4 The HR HPV genotypes express two major transforming genes that code for the E6 and E7 proteins, which are required for the immortalization of human primary genital keratinocytes. 5 These two oncogenes are uniformly retained and highly expressed in cervical cancer cells, and their continuous expression is required for retention of
Background: More than 13,0 0 0 cases were reported to be infected with COVID-19 by RT-PCR in South Korea. Most studies report clinical characteristics of hospitalized patients with COVID-19; the full spectrum of disease severity has thus not yet been well described.Methods: Using retrospective observational methods, this study analyzed factors affecting early clinical symptoms, clinical progress, and severity of disease for COVID-19 positive patients released from quarantine to provide information on establishing optimized care for new patients. The medical data of 7803 laboratory-confirmed patients who had been discharged or died by April 30, 2020 were analyzed using multivariate logistic regression analysis.Findings: On admission, 7383 (94 • 5%) patients were asymptomatic or showed mild illness, and 372 (4 • 8%) patients were severe illness. Also, 48 (0 0 • 6%) were hospitalized with critically ill when diagnosed. Most patients with asymptomatic or mild illness on admission remained mild until discharge, 253 (3 • 4%) progressed to severe illness, and 83 (1 • 1%) died in hospital. However, the case fatality were 29 • 8% and 62 • 5% in severe and critically ill patients, respectively. At admission, 73 • 0% of hospitalized patients had symptoms; most common were cough (42 • 5%), sputum (28 • 8%), and fever (20 • 1%). Only 35 • 2% of laboratory confirmed patients admitted to the temporary care facility complained of symptoms. Increasing odds of being critically ill was associated with older age (OR 28 • 93, 95% CI 13 • 34-62 • 75 for age > 70y, vs. age < 50 y; p < 0 • 0 0 01), being male (OR 2 • 15, 95% CI1 • 59-2 • 89; p < 0 • 0 0 01), fever (OR 2 • 52, 95% CI 1.84-3 • 45; p < 0 • 0 0 01), and shortness of breath (OR 7 • 40, 95% CI 5 • 37-10 • 19; p < 0 • 0 0 01). Comorbid illness significantly increased risk of critical illness or death.Interpretation: Most cases were discharged as asymptomatic or recovered from mild illness, and only 9 • 7% developed severe disease requiring oxygen therapy or more. Case fatality rate was 2 • 9%, and markedly increased in those over age 50. Risk factors such as age, sex, fever, shortness of breath, and underlying disease can be useful in predicting future clinical severity. Additionally, the number of confirmed asymptomatic COVID-19 patients significantly contribute to continued spread.
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