HMGB3 is a potential diagnostic marker for early cervical lesion screening.
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ABSTRACT:
SUBMITTER: Cui Q
PROVIDER: S-EPMC10404999 | biostudies-literature | 2023 Nov
REPOSITORIES: biostudies-literature
Publications
HMGB3 is a potential diagnostic marker for early cervical lesion screening.
Cui Qianwen Q Zhao Jiarong J Deng Qingmei Q Liu Yu Y Fu Changfang C Wu Qiang Q Sun Qiuyan Q Weng Haiyan H Dai Haiming H Yang Wulin W
Genes & diseases 20230327 6
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Project description:1. The expression of plasma exosomal ncRNAs and mRNAs was compared a group of 12 samples from healthy individuals (normal group) with a group of 30 samples from cervical cancer patients before primary concurrent chemoradiotherpay (cancer group) using differentially expressed gene (DEG) analysis. The RNAs with both |log2FC| >2 and P values < 0.05 2. We prepared for log2 fold change values of plasma exosomal RNAs for 30 patients from 30 samples in second week during CCRT compared with those before treatment to screen secondary biological function of primarily selected DEGs. We analyzed the association between non-coding RNA (ncRNA)-mRNA network and cancer using ingenuity pathway analysis after secondary selection according to the number and correlation of mRNAs (or ncRNAs) relevant to log2FC in the expression of primarily selected ncRNAs (or mRNAs) before and after CCRT. The raw NGS data of 58 samples from 29 patients were uploaded in E-MTAB-10215. Here we will upload raw RNA sequencing data of 12 samples from 12 healthy individuals and 2 samples from one cervical cancer patient.
2022-12-01 | E-MTAB-10930 | biostudies-arrayexpress
Project description:BackgroundRadiotherapy is regarded as a milestone for the cure of cervical cancer. However, clinical outcome heavily be hindered by radioresistance. So, exploring the underlying mechanism of radioresistance, and find potential target, well deserve fully emphasis.MethodsIn this study, we developed two novel radiation resistance cervical cancer cell lines, which could mimic clinical radioresistance. In order to find new potential targets, RNA-Seq, database analysis, streptavidin-agarose and LC/MS were used. Pull-down, luciferase and rescue assays were conducted to explore the regulatory mechanisms. To further evaluate the correlation between therapeutic responses and HMGB3/hTERT expression, 172 cervical cancer patients were recruited.ResultsKnockdown of HMGB3 significantly inhibit the DNA damage repair and induced more γH2AX foci, leading to enhanced chemo- and radio-sensitivity in vitro and in vivo, whereas HMGB3 overexpression has the opposite effects. HMGB3 promotes cell growth and radioresistance by transcriptionally up-regulating hTERT via the specifical binding of HMGB3 at the hTERT promoter region from - 902 to - 321. HMGB3 knockdown-mediated radiosensitization could be reversed by the overexpressed hTERT in both cervical cancer cell lines and xenograft tumor mouse model. Furthermore, clinical data from 172 cervical cancer patients proved that there was a positive correlation between HMGB3 and hTERT expression, and high expression of HMGB3/hTERT predicted poor response to radiotherapy, worse TNM stages and shorter survival time.ConclusionHere, we have identified HMGB3/hTERT signaling axis as a new target for cervical cancer radioresistance. Our results provide new insights into the mechanism of cervical cancer radioresistance and indicate that targeting the HMGB3/hTERT signaling axis may benefit cervical cancer patients.
| S-EPMC7664109 | biostudies-literature
Project description:ObjectiveThis study assessed perceived barriers, precancerous cervical lesion screening acceptance, and associated factors among women in Eastern Ethiopia.SettingThis study was conducted in Hiwot Fana Specialized Hospital and Jugal Hospital.Study designThis study is a facility-based cross-sectional study.Study participantsThis study included 1181 women aged 25-49 years. Bivariate and multivariable logistic regression was used to evaluate the relationship between variables and control confounders.ResultsNearly half of the participants (587 or 49.7%) agreed to be screened for precancerous cervical lesions. Seventy-six per cent of those checked were negative for visual inspection with acetic acid, 18.5% were positive, and 5.7% had cancer-like lesions. In multivariable analysis, fear of discomfort from the screening procedure, having a male screener, and embarrassment were the perceived barriers that were inversely associated with screening acceptance.ConclusionsThe uptake of the screening service in the study area was not satisfactory, indicating that the programme was underutilised in the area.
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Project description: Not available
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Project description:microRNAs (miRNAs) play important roles in regulation of gene expression during cervical carcinogenesis. We investigated expression profiles of miRNAs in cervical cancer and its precursor lesions by utilizing cervical mucus. Cervical mucus was collected from 230 patients with a normal cervix, cervical intraepithelial neoplasia (CIN), squamous cell carcinoma (SCC), or adenocarcinoma (AD). The levels of miRNA in the mucus were quantified by miRNA array and real-time reverse-transcriptase polymerase chain reaction (RT-PCR). The performance for detecting diseases was statistically analysed. The expression of miRNAs was further validated in the surgical tissues of enrolled patients. Four miRNAs (miR-126-3p, -20b-5p, -451a, and -144-3p) were significantly up-regulated in SCC and AD compared with normal, and their expression levels correlated with disease severity and high-risk human papillomavirus infection. Receiver operating characteristic curve analyses revealed that the area under the curve values for miR-126-3p, -20b-5p, -451a, and -144-3p were 0.89, 0.90, 0.94, and 0.93, respectively, for SCC plus AD compared with normal, showing high accuracy of cancer detection. Real-time RT-PCR analyses confirmed the expression of these four miRNAs in frozen tissues from cervical cancer. miR-126-3p, -20b-5p, -451a, and -144-3p in cervical mucus are promising biomarkers for cervical cancer and high-grade CINs.
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Project description:Parkinson's disease (PD) is the second most common neurodegenerative disorder and has profound impacts on the daily lives of patients. However, there is a lack of effective biomarkers for early diagnosis, and the mechanisms of PD pathogenesis remain obscure. microRNAs (miRNAs) are post-transcriptional gene regulators and can be easily detected in plasma, which suggests a promising role as diagnostic markers. Here, we aimed to explore a peripheral biomarker, which not only can be applied for early diagnosis of PD but also has the potential to be a therapeutic target. Through miRNA microarray screening and further validation in plasma from 169 sporadic PD patients, 170 healthy controls, and 60 essential tremor (ET) patients, hsa-miR-4639-5p level was identified to be significantly up-regulated in PD patients. Also, it was able to discriminate between early PD patients (disease duration ≤2 years or Hoehn and Yahr stage 1-2.5) and healthy controls. Furthermore, hsa-miR-4639-5p was shown to negatively regulate DJ-1 (PARK7), a well-known PD-related gene, in the post-transcriptional level. Abnormal up-regulation of hsa-miR-4639-5p caused down-regulation of DJ-1 protein level, leading to severe oxidative stress and neuronal death. In conclusion, hsa-miR-4639-5p has the potential to be a peripheral diagnostic biomarker and therapeutic target for early PD.
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Project description:S100A4 protein overexpression has been reported in different types of cancer and plays a key role by interacting with the tumor suppressor protein Tp53. Single nucleotide polymorphisms (SNP) in S100A4 could directly influence the biomolecular interaction with the tumor suppressor protein Tp53 due to their aberrant conformations. Hence, the study was designed to predict the deleterious SNP and its effect on the S100A4 protein structure and function. Twenty-one SNP data sets were screened for nonsynonymous mutations and subsequently subjected to deleterious mutation prediction using different computational tools. The screened deleterious mutations were analyzed for their changes in functionality and their interaction with the tumor suppressor protein Tp53 by protein-protein docking analysis. The structural effects were studied using the 3DMissense mutation tool to estimate the solvation energy and torsion angle of the screened mutations on the predicted structures. In our study, 21 deleterious nonsynonymous mutations were screened, including F72V, E74G, L5P, D25E, N65S, A28V, A8D, S20L, L58P, and K26N were found to be remarkably conserved by exhibiting the interaction either with the EF-hand 1 or EF-hand 2 domain. The solvation and torsion values significantly deviated for the mutant-type structures with S20L, N65S, and F72L mutations and showed a marked reduction in their binding affinity with the Tp53 protein. Hence, these deleterious mutations might serve as prospective targets for diagnosing and developing personalized treatments for cancer and other related diseases.
| S-EPMC9357733 | biostudies-literature
Project description:This study aims to evaluate HR-HPV viral load in the cervical lesion assessment and its diagnostic value on the triage of ASCUS. The three-step protocol for cervical cancer screening was carried out in 5171 patients from June 2017 to August 2019, and 1620 histopathological results were obtained. The positive rate of HR-HPV and TCT increased with the aggravation of pathological grades of cervical lesions. The sensitivity and specificity of HR-HPV (DH3) to detect CIN II+ were 91.91% and 84.46%, respectively. In comparison, the corresponding results of the cytology test were 80.51% and 83.12%. HPV16/18 viral load was positively correlated with the grade of cervical lesions (p < 0.001, r = 0.321). The diagnostic efficiency of AUC by applying HPV16/18 viral load was 0.682 for the diagnosis of CIN II+. The optimal HPV16/18 viral load for predicting CIN II+ was 6.80 RLU/CO (relative light units/cut-off), with corresponding sensitivity of 48.6%, specificity of 79.7%, and Youden index of 0.283. In the ASCUS population, viral loads were statistically different in HPV16/18 and the other 12 HR-HPV when compared cervicitis group with CIN I group and CIN II+ group (all p < 0.05). Statistical differences were detected concerning HPV16/18 viral load, contact bleeding status, and smoking status when compared cervicitis group with CIN I group and CIN II+ group (p < 0.05), with a corresponding odds ratio of 1.004, 1.533, and 5.513, respectively. Our findings suggest that HR-HPV viral load can be regarded as a useful tool to predict the grade of cervical lesions for ASCUS triage. ClinicalTrials.gov ID: NCT03178136.
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Project description:Many factors need to be considered when planning and managing a screening programme for the early detection of cervical cancer (CC). A non-systematic international review of the organisation of CC screening using high-risk human papillomavirus (HPV-HR) testing, aimed at identifying the organisational methods of these programmes, was conducted with a view to supporting the future of the French system in the context of the transition to HPV-HR testing. In countries where HPV testing has been implemented or planned, the initial reflection process has provided an opportunity to rethink the previous (cytological) screening organisation. Despite considerable differences between countries, a nationally or regionally centralised organisational model appears to be the preferred option in most countries. This model is based on a national/regional structure tasked with all invitations, reminders, follow-up and coordination, centralised laboratories integrating both biology and pathology laboratories, and a unified information system integrated with routine health management tools used by health practitioners and nurses. Besides quality considerations, grouped purchasing makes it possible to implement a public procurement policy that includes price negotiations with suppliers. Discussions around the introduction of HPV testing have resulted in most countries reviewing or creating information systems and quality assurance processes. While the WHO seems to recommend the systematic use of vaginal self-sampling, very few countries have considered this option. More and more countries are planning to implement vaginal self-sampling, but no clear organisational model has emerged from the countries where it has been implemented to date.
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Project description:Observation of tongue coating, a foundation for clinical diagnosis and treatment in traditional Chinese medicine (TCM), is a major indicator of the occurrence, development, and prognosis of disease. The biological basis of tongue diagnosis and relationship between the types and microorganisms of tongue coating remain elusive. Thirteen chronic erosive gastritis (CEG) patients with typical yellow tongue coating (YTC) and ten healthy volunteers with thin white tongue coating (WTC) were included in this study. Patients were provided a 2-course targeted treatment of a herbal medicine Ban Xia Xie Xin decoction, traditionally prescribed for CEG patients with YTC, to evaluate the relationship between tongue coating microbiota and diagnosis of CEG with typical YTC. The tongue coating segregation structure was determined using Illumina Miseq sequencing of the V4-V5 region of the 16S ribosomal RNA gene. Bacillus was significantly observed only in CEG patients with YTC, but not in patients who received the decoction. YTC (n = 22) and WTC (n = 29) samples were collected for bacterial culturing to illustrate the relationship between Bacillus and YTC. The Bacillus positivity rate of YTC samples was 72.7%; Bacillus was not observed in WTC samples. In conclusion, Bacillus was strongly associated with YTC.
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