Hypermethylated PCDHGB7 as a universal cancer only marker and its application in early cervical cancer screening.
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ABSTRACT:
SUBMITTER: Dong S
PROVIDER: S-EPMC8214855 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND: Tumor-derived aberrantly methylated DNA might serve as diagnostic biomarkers for cancer, but so far, few such markers have been identified. The aim of the present study was to investigate the potential of the MAL (T-cell differentiation protein) gene as an early epigenetic diagnostic marker for colorectal tumors. METHODS: Using methylation-specific polymerase chain reaction (MSP) the promoter methylation status of MAL was analyzed in 218 samples, including normal mucosa (n = 44), colorectal adenomas (n = 63), carcinomas (n = 65), and various cancer cell lines (n = 46). Direct bisulphite sequencing was performed to confirm the MSP results. MAL gene expression was investigated with real time quantitative analyses before and after epigenetic drug treatment. Immunohistochemical analysis of MAL was done using normal colon mucosa samples (n = 5) and a tissue microarray with 292 colorectal tumors. RESULTS: Bisulphite sequencing revealed that the methylation was unequally distributed within the MAL promoter and by MSP analysis a region close to the transcription start point was shown to be hypermethylated in the majority of colorectal carcinomas (49/61, 80%) as well as in adenomas (45/63, 71%). In contrast, only a minority of the normal mucosa samples displayed hypermethylation (1/23, 4%). The hypermethylation of MAL was significantly associated with reduced or lost gene expression in in vitro models. Furthermore, removal of the methylation re-induced gene expression in colon cancer cell lines. Finally, MAL protein was expressed in epithelial cells of normal colon mucosa, but not in the malignant cells of the same type. CONCLUSION: Promoter hypermethylation of MAL was present in the vast majority of benign and malignant colorectal tumors, and only rarely in normal mucosa, which makes it suitable as a diagnostic marker for early colorectal tumorigenesis.
| S-EPMC2292685 | biostudies-literature
Project description:Transvaginal measurement of cervical length (CL) has been advocated as a screening tool to prevent preterm birth, but controversy remains regarding the overall utility of universal screening.We aimed to evaluate the acceptability of a universal CL screening program. Additionally we evaluated risk factors associated with declining screening and subsequent delivery outcomes of women who accepted or declined screening.This was a retrospective cohort study of transvaginal CL screening at a single institution from July 1, 2011, through December 31, 2014. Institutional protocol recommended transvaginal CL measurement at the time of anatomic survey between 17-23 weeks in all women with singleton, viable pregnancies, without current or planned cerclage, with patients able to opt out. Patients with CL ?20 mm were considered to have clinically significant cervical shortening and were offered treatment. We assessed acceptance rate, risk factors for declining CL screening, and the trend of acceptance of CL screening over time. We also calculated the prevalence of CL ?25, ?20, and ?15 mm, and estimated the association between CL screening and spontaneous preterm birth.Of 12,740 women undergoing anatomic survey during the study period, 10,871 (85.3%; 95% confidence interval [CI], 84.7-85.9%) underwent CL screening. Of those, 215 (2.0%) had a CL ?25 mm and 131 (1.2%) had a CL ?20 mm. After the first 6 months of implementation, there was no change in rates of acceptance of CL screening over time (P for trend = .15). Women were more likely to decline CL screening if they were African American (adjusted odds ratio [aOR], 2.17; 95% CI, 1.93-2.44), obese (aOR, 1.18; 95% CI, 1.06-1.31), multiparous (aOR, 1.45; 95% CI, 1.29-1.64), age <35 years (aOR, 1.24; 95% CI, 1.08-1.43), or smokers (aOR, 1.42; 95% CI, 1.20-1.68). Rates of spontaneous preterm birth <28 weeks were higher in those who declined CL screening (aOR, 2.01; 95% CI, 1.33-3.02).Universal CL screening was implemented successfully with 85% of women screened. Overall incidence of short cervix was low and women with significant risk factors for preterm birth were more likely to decline screening. Patients who declined CL screening were more likely to be African American, obese, multiparous, age <35 years, and smokers. Rates of early, but not late, spontaneous preterm birth were significantly higher among women who did not undergo CL screening.
| S-EPMC4810783 | biostudies-literature
Project description:Endometrial cancer (EC) is one of the most common gynecologic cancers in developed countries. Presently, it is imperative to develop a reliable, noninvasive, or minimally invasive detection method for EC. We explored the possibility of using DNA methylation marker from endometrial brush samples (with a "Tao brush") and cervical scrapes (with a "Pap brush") for early detection of EC. We analyzed the methylation data of EC and normal endometrial tissues from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data sets. An optimized methylation-sensitive restriction enzyme combined with real-time fluorescent quantitative PCR (MSRE-qPCR) was used for methylation detection. Included in the training set were 143 endometrial tissues, 103 Tao, and 109 Pap brush samples. The validation set included 110 Tao and 112 Pap brush samples. PCDHGB7 was significantly hypermethylated in EC compared with normal endometrial tissues in the TCGA and GEO data sets (AUC >0.95), which was verified in clinical samples. In the Pap brush samples, the AUC was 0.86 with 80.65% sensitivity and 82.81% specificity, whereas the Tao brush samples exhibited higher specificity (95.31%). The combination of Tao and Pap brush samples significantly increased the sensitivity to 90.32%. In the validation set, the final model yielded a sensitivity of 98.61%, specificity of 60.53%, positive predictive value of 82.56%, and negative predictive value of 95.83%. These results demonstrate the potential application of the novel methylation marker, hypermethylated PCDHGB7, in cervical scrapings and endometrial brush, which provides a viable, noninvasive, or minimally invasive method for early endometrial cancer detection across different clinical features and histologies to supplement current hysteroscopy diagnosis.
| S-EPMC8763697 | biostudies-literature
Project description:This paper investigates the effect of expansion to near-universal health insurance coverage in Massachusetts on breast and cervical cancer screening. We use data from 2002 to 2010 to compare changes in receipt of mammograms and Pap tests in Massachusetts relative to other New England states. We also consider the effect specifically among low-income women. We find positive effects of Massachusetts health reform on cancer screening, suggesting a 4 to 5% increase in mammograms and 6 to 7% increase in Pap tests annually. Increases in both breast and cervical cancer screening are larger 3 years after the implementation of reform than in the year immediately following, suggesting that there may be an adjustment or learning period. Low-income women experience greater increases in breast and cervical cancer screening than the overall population; among women with household income less than 250% of the federal poverty level, mammograms increase by approximately 8% and Pap tests by 9%. Overall, Massachusetts health reform appears to have increased breast and cervical cancer screening, particularly among low-income women. Our results suggest that reform was successful in promoting preventive care among targeted populations.
| S-EPMC4540679 | biostudies-literature
Project description:ObjectiveEvaluate the significance of BMRT HPV assay viral load and its performance for secondary screening.MethodsBMRT-HPV reports type-specific viral loads/10,000 cells. We tested 1,495 physician collected, stored specimens from Chinese Multiple-center Screening Trial (CHIMUST), that were positive by Cobas, SeqHPV, and/or Cytology (≥LSIL); and 2,990 age matched, negatives in a nested case control study. We explored the relationship between BMRT HR-HPV viral load and cervical lesions, determined alternative CIN2+ cut-points by ROC curve, and evaluated BMRT HR-HPV for primary / secondary cervical cancer screening.ResultsThe viral loads of HPV16/18, 12 other subtypes HR-HPV and 14 HR-HPV were statistically different in all grades of cervical lesions (P<0.05, among which HPV16, 33 and 58 showed the strongest relationship (P<0.01). The viral load of HR-HPV also increased with the grade of cervical lesions (P<0.05). The sensitivity for CIN2+ and CIN3+ of BMRT was comparable to Cobas (92.6% vs 94.3%, 100% vs 100%, P>0.05), specificity was higher than Cobas (84.8% vs 83.3%, 83.5% vs 82.0%, P<0.001). When using HPV16/18 viral load(log cut-point ≥3.2929), plus the viral-load of 12 other subtypes (log cut-point ≥3.9625) as secondary triage, compared with Cobas HPV16/18+ plus cytology ≥ASC-US as triage, the sensitivities for CIN2+ and CIN3+ were similar (P>0.05). However, the BMRT HR-HPV viral load combined with subtypes did not require cytology.ConclusionBMRT is as sensitive as Cobas4800 for primary cervical cancer screening. BMRT HR-HPV viral load combined with subtypes can be used as a secondary strategy for cervical cancer screening, especially for areas with insufficient cytological resources.
| S-EPMC7194433 | biostudies-literature
Project description:The optimal schedules for breast cancer screening in terms of examination frequency and ages at examination are of practical interest. A decision-theoretic approach is explored to search for optimal cancer screening programs which should achieve maximum survival benefit while balancing the associated cost to the health care system. We propose a class of utility functions that account for costs associated with screening examinations and value of survival benefit under a non-stable disease model. We consider two different optimization criteria: optimize the number of screening examinations with equal screening intervals between exams but without a pre-fixed total cost; and optimize the ages at which screening should be given for a fixed total cost. We show that an optimal solution exists under each of the two frameworks. The proposed methods may consider women at different levels of risk for breast cancer so that the optimal screening strategies will be tailored according to a woman's risk of developing the disease. Results of a numerical study are presented and the proposed models are illustrated with various data inputs. We also use the data inputs from the Health Insurance Plan of New York (HIP) and Canadian National Breast Screening Study (CNBSS) to illustrate the proposed models and to compare the utility values between the optimal schedules and the actual schedules in the HIP and CNBSS trials. Here, the utility is defined as the difference in cure rates between cases found at screening examinations and cases found between screening examinations while accounting for the cost of examinations, under a given screening schedule.
| S-EPMC3230228 | biostudies-literature
Project description:PurposeTo estimate the cost-effectiveness of breast cancer screening in the National Breast and Cervical Cancer Early Detection Program (NBCCEDP).MethodsUsing a modified CISNET breast cancer simulation model, we estimated outcomes for women aged 40-64 years associated with three scenarios: breast cancer screening within the NBCCEDP, screening in the absence of the NBCCEDP (no program), and no screening through any program. We report screening outcomes, cost, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), and sensitivity analyses results.ResultsCompared with no program and no screening, the NBCCEDP lowers breast cancer mortality and improves QALYs, but raises health care costs. Base-case ICER for the program was $51,754/QALY versus no program and $50,223/QALY versus no screening. Probabilistic sensitivity analysis ICER for the program was $56,615/QALY [95% CI $24,069, $134,230/QALY] versus no program and $51,096/QALY gained [95% CI $26,423, $97,315/QALY] versus no screening.ConclusionsOn average, breast cancer screening in the NBCCEDP was cost-effective compared with no program or no screening.
| S-EPMC6613985 | biostudies-literature
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:BACKGROUND:Visual inspection after application of acetic acid (VIA) and Lugol's iodine (VILI) is a cervical cancer (CC) screening approach that has recently been adopted in low- and middle-income countries (LMIC). Innovative technologies allow the acquisition of consecutive cervical images of VIA and VILI using a smartphone application. The aim of this study was to evaluate the quality of smartphone images in order to assess the feasibility and usability of a mobile application for CC screening in LMIC. METHODS:Between May and November 2015, women aged 30-65 years were recruited in a CC screening campaign in Madagascar. Human papillomavirus-positive women were invited to undergo VIA/VILI assessment. Pictures of their cervix were taken using a Samsung Galaxy S5 with an application called "Exam", which was designed to obtain high-quality images and to classify them in the following sequence: native, VIA, VILI and posttreatment. Experts in colposcopy were asked to evaluate if the quality of the pictures was sufficient to establish the diagnosis and to assess sharpness, focus and zoom. RESULTS:The application use was simple and intuitive, and 208 pictures were automatically classified and recorded in the patient's file. The quality was judged as adequate for diagnosis in 93.3% of cases. The interobserver agreement was ? =0.45 (0.23-0.58), corresponding to a moderate agreement on the common scale of kappa values. CONCLUSION:This smartphone application allows the acquisition of good quality images for VIA/VILI diagnosis. The classification of images in a patient database makes them accessible to on- and off-site experts, and allows continuous clinical education. Smartphone applications may offer an alternative to colposcopy for CC screening in LMIC.
| S-EPMC5489054 | biostudies-literature
Project description:BackgroundWomen with a history of incarceration bear a disproportionate burden of cervical disease and have special characteristics that affect their intent and/or ability to adhere to cervical screening and follow-up recommendations. The goal of this study was to identify factors associated with cervical cancer screening and screening outcomes among incarcerated women.MethodsWe applied a framework of predisposing factors, enabling factors and population-specific characteristics that could impact screening behaviors and outcomes for this population. We used bivariate chi-square tests and Wilcoxon signed-rank tests to analyze data previously collected from 290 incarcerated women.ResultsCervical cancer screening belief score, as a predisposing factor, was associated with women who had an up-to-date Pap test and who had a cervical cancer diagnosis ever in their life. Both a sexual history containing high-risk behaviors and a history of abuse, population-specific factors, were each associated with having had an abnormal pap; mental health, incarceration, and substance use histories were each associated with having a diagnosis of cervical cancer.ConclusionsThe significant differences in outcomes for these population-specific factors suggest the need for a health services approach that addresses the challenges to the cervical cancer preventive health needs of incarcerated women.Implications for practiceProviders working with vulnerable populations such as women who have been incarcerated should be aware that their risk histories have an influence on their follow-up behaviors. These women will need extra support for cervical cancer screening and follow-up care.
| S-EPMC6019745 | biostudies-literature