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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.

MicroRNAs are reported as promising biomarkers for the diagnosis and treatment of breast cancer. miR‐1260b is identified as a tumor‐associated noncoding microRNA in other cancers, although the role of miR‐1260b and its clinical relevance in breast cancer remain unclear. In this study, miR‐1260b as a potential prognostic biomarker was observed by univariate and multivariate Cox regression analyses in 102 breast tumor tissues. The tumorigenic role of miR‐1260b in terms of proliferation, apoptosis, and migration of breast cancer cells was investigated using gain‐ and loss‐of‐function assays in vitro. Additionally, the potential early diagnosis and treatment monitoring marker of miR‐1260b was validated in 129 plasma samples. We found that high miR‐1260b expression was markedly associated with bulky tumor size, advanced stage, and lymph node invasion. Particularly, the high–miR‐1260b‐expression group showed shorter overall survival than the low–miR‐1260b‐expression group. The inhibition of oncogenic miR‐1260b induced apoptosis and decreased migration and invasion of MDA‐MB‐231 cells. CASP8 was revealed as a direct target gene of miR‐1260b, which is closely related to apoptosis. Furthermore, miR‐1260b expression levels in plasma were significantly higher in patients with breast cancer than in healthy controls. The patients who tested positive for miR‐1260b showed 16.3‐ and 18.2‐fold higher risks in the early stage and locally advanced stage, respectively, compared with healthy controls, and the risk was decreased 6.2‐fold after neoadjuvant chemotherapy. Taken together, miR‐1260b may be a potential novel diagnostic, prognostic, and therapeutic target in breast cancer. High miR‐1260b expression was markedly associated with bulky tumor size, advanced stage, and lymph node invasion. Particularly, the high–miR‐1260b‐expression group showed shorter overall survival than the low–miR‐1260b‐expression group. The inhibition of oncogenic miR‐1260b induced apoptosis and decreased migration and invasion of MDA‐MB‐231 cells. CASP8 was revealed as a direct target gene of miR‐1260b, which is closely related to apoptosis.

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.

Background A comprehensive understanding of excess mortality for patients with underlying conditions during the COVID-19 pandemic has yet to be achieved. Thus, this study aims to investigate excess mortality and healthcare costs during the COVID-19 pandemic among patients with ten major chronic diseases in South Korea. Methods A nationwide retrospective cohort study used the Korea Disease Control and Prevention Agency-COVID-19-National Health Insurance Service (K-CoV-N) database, integrating COVID-19 testing, vaccination, mortality, and insurance claims data for the entire Korean population. We assessed mortality and medical costs from 2017 to 2022 in patients with ten chronic conditions, including chronic lung disease (CLD), heart disease, stroke, diabetes, hypertension, chronic liver disease, autoimmune disorders, chronic kidney disease (CKD), dementia/Parkinson’s disease (DPD), and cancer. Multivariable logistic and negative binomial regression were used to compare mortality and costs between the pre-pandemic (2019–2019) and pandemic periods (2020–2022), stratified by COVID-19 infection status and vaccination history. Results Mortality rates increased significantly during the pandemic for CLD, stroke, chronic liver disease, autoimmune disease, CKD, and DPD (adjusted odds ratio (aOR) > 1.00 and p  < 0.05). In contrast, mortality decreased for diabetes, hypertension, and cancer (aOR < 1.00 and p  < 0.001). Healthcare costs also exhibited disease-specific trends, with increased spending for conditions such as CLD and autoimmune diseases, but reduced costs for diseases like stroke and DPD. Notably, diabetes, hypertension, and cancer showed decreased mortality despite rising healthcare expenditures, highlighting the role of medical innovation and advancements in chronic disease management. Conclusions This study underscores the heightened vulnerability of patients with chronic conditions during pandemics and reveals the possibility of disparities in healthcare access and resource allocation. These findings offer critical insights for future public health strategies and policy development to mitigate the impact of health crises on individuals with chronic diseases. Clinical trial This study does not include a clinical trial (Number: not applicable).

p63 is a transcription factor p53 family. Two major isoforms of p63, TAp63 with transactivation (TA) domain and ΔNp63 with truncated TA domain, have been reported to play opposing roles either in tumor suppression or oncogenic function. Little is known about the association of these two isoforms of p63 in the carcinogenesis of cervical cancer. In this study, the mRNA expression levels of TAp63 and ΔNp63 in 40 normal, 30 low-grade squamous intraepithelial lesions (LSIL), 38 high-grade squamous intraepithelial lesions (HSIL), and 52 cervical cancer formalin-fixed paraffin-embedded tissues were examined using quantitative reverse transcription polymerase chain reaction (RT-qPCR). We analyzed the association between the ΔNp63 and ΔN/TAp63 mRNA expression ratio and clinicopathological parameters and compared disease-specific survival of each ΔNp63 mRNA expression and ΔN/TAp63 mRNA expression ratio. The ΔN/TAp63 mRNA expression ratio in cervical cancer showed higher sensitivity than the mRNA expression levels of ΔNp63 (52.0% vs 44.2%). The level of ΔN/TAp63 mRNA expression ratio in precancerous LSIL and HSIL was higher than in normal tissues (P = 0.01 and P = 0.003) and lower than in cervical cancer tissues (P = 0.03 and P = 0.02). Besides, the positive ΔN/TAp63 mRNA expression ratio was associated with bulky tumor size and high expression of Ki-67, the proliferation marker, in cervical cancer (P = 0.04 and P = 0.02). The cervical cancer patients with the positive ΔN/TAp63 mRNA expression ratio showed worse survival compared to those who with the negative expression ratio of ΔN/TAp63 (HR = 5.7, 95% CI: 1.6-19.9). In conclusion, the balance of TAp63 and ΔNp63 is closely related to the carcinogenesis of cervical cancer. The ΔN/TAp63 mRNA expression ratio could be useful as a diagnostic and prognostic marker of cervical cancer.

[This corrects the article DOI: 10.1371/journal.pone.0214867.].

MicroRNAs are reported as promising biomarkers for the diagnosis and treatment of breast cancer. miR-1260b is identified as a tumor-associated noncoding microRNA in other cancers, although the role of miR-1260b and its clinical relevance in breast cancer remain unclear. In this study, miR-1260b as a potential prognostic biomarker was observed by univariate and multivariate Cox regression analyses in 102 breast tumor tissues. The tumorigenic role of miR-1260b in terms of proliferation, apoptosis, and migration of breast cancer cells was investigated using gain- and loss-of-function assays in vitro. Additionally, the potential early diagnosis and treatment monitoring marker of miR-1260b was validated in 129 plasma samples. We found that high miR-1260b expression was markedly associated with bulky tumor size, advanced stage, and lymph node invasion. Particularly, the high-miR-1260b-expression group showed shorter overall survival than the low-miR-1260b-expression group. The inhibition of oncogenic miR-1260b induced apoptosis and decreased migration and invasion of MDA-MB-231 cells. CASP8 was revealed as a direct target gene of miR-1260b, which is closely related to apoptosis. Furthermore, miR-1260b expression levels in plasma were significantly higher in patients with breast cancer than in healthy controls. The patients who tested positive for miR-1260b showed 16.3- and 18.2-fold higher risks in the early stage and locally advanced stage, respectively, compared with healthy controls, and the risk was decreased 6.2-fold after neoadjuvant chemotherapy. Taken together, miR-1260b may be a potential novel diagnostic, prognostic, and therapeutic target in breast cancer.

p63 is a transcription factor p53 family. Two major isoforms of p63, TAp63 with transactivation (TA) domain and [DELTA]Np63 with truncated TA domain, have been reported to play opposing roles either in tumor suppression or oncogenic function. Little is known about the association of these two isoforms of p63 in the carcinogenesis of cervical cancer. In this study, the mRNA expression levels of TAp63 and [DELTA]Np63 in 40 normal, 30 low-grade squamous intraepithelial lesions (LSIL), 38 high-grade squamous intraepithelial lesions (HSIL), and 52 cervical cancer formalin-fixed paraffin-embedded tissues were examined using quantitative reverse transcription polymerase chain reaction (RT-qPCR). We analyzed the association between the [DELTA]Np63 and [DELTA]N/TAp63 mRNA expression ratio and clinicopathological parameters and compared disease-specific survival of each [DELTA]Np63 mRNA expression and [DELTA]N/TAp63 mRNA expression ratio. The [DELTA]N/TAp63 mRNA expression ratio in cervical cancer showed higher sensitivity than the mRNA expression levels of [DELTA]Np63 (52.0% vs 44.2%). The level of [DELTA]N/TAp63 mRNA expression ratio in precancerous LSIL and HSIL was higher than in normal tissues (P = 0.01 and P = 0.003) and lower than in cervical cancer tissues (P = 0.03 and P = 0.02). Besides, the positive [DELTA]N/TAp63 mRNA expression ratio was associated with bulky tumor size and high expression of Ki-67, the proliferation marker, in cervical cancer (P = 0.04 and P = 0.02). The cervical cancer patients with the positive [DELTA]N/TAp63 mRNA expression ratio showed worse survival compared to those who with the negative expression ratio of [DELTA]N/TAp63 (HR = 5.7, 95% CI: 1.6-19.9). In conclusion, the balance of TAp63 and [DELTA]Np63 is closely related to the carcinogenesis of cervical cancer. The [DELTA]N/TAp63 mRNA expression ratio could be useful as a diagnostic and prognostic marker of cervical cancer.

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: In this study, the CervicGen HPV RT-qDX assay (Optipharm, Osong, Republic of Korea), which detects 16 HPV high-risk subtypes (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, and 69), and the CervicGen hTERT RT-qDX assay (Optipharm) were evaluated using 545 ThinPrep (Hologic, Bedford, MA) Papanicolaou samples. 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, high-grade squamous intraepithelial lesions (HSILs), atypical squamous cells—cannot 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.