Ovarian cancer (OC) poses a significant health risk to women worldwide, with late diagnoses and chemotherapy resistance leading to high mortality rates. Despite several histological subtypes, the primary challenge remains the subtle nature of its symptoms, resulting in advanced-stage diagnosis and reduced treatment success rates. With platinum-based therapies showing relative efficacy but limited survival enhancements, the emergence of chemotherapy resistance during recurrence remains a critical obstacle.
View Article and Find Full Text PDFCervical cancer is the one of the most common gynecology malignancies in the world. National Comprehensive Cancer Network (NCCN) guidelines on cervical cancer are widely adopted as national guidelines and clinical practice guidelines. These guidelines are constantly being updated but their effectiveness has not been questioned.
View Article and Find Full Text PDFCell-free microRNA (miRNA) in biofluids released by tumors in either protein or vesicle-bound form, represent promising minimally-invasive cancer biomarkers. However, a highly abundant non-tumor background in human plasma and serum complicates the discovery and detection of tumor-selective circulating miRNAs. We performed small RNA sequencing on serum and plasma RNA from Nasopharyngeal Carcinoma (NPC) patients.
View Article and Find Full Text PDFOffering self-sampling for HPV testing improves the effectiveness of current cervical screening programs by increasing population coverage. Molecular markers directly applicable on self-samples are needed to stratify HPV-positive women at risk of cervical cancer (so-called triage) and to avoid over-referral and overtreatment. Deregulated microRNAs (miRNAs) have been implicated in the development of cervical cancer, and represent potential triage markers.
View Article and Find Full Text PDFIntroduction: To evaluate the performance of hypermethylation analysis of ASCL1, LHX8 and ST6GALNAC5 in physician-taken cervical scrapes for detection of cervical cancer and cervical intraepithelial neoplasia (CIN) grade 3 in women living with HIV (WLHIV) in South Africa.
Methods: Samples from a prospective observational cohort study were used for these analyses. Two cohorts were included: a cohort of WLHIV who were invited for cervical screening (n = 321) and a gynaecologic outpatient cohort of women referred for evaluation of abnormal cytology or biopsy proven cervical cancer (n = 108, 60% HIV seropositive).
Cervical cancer development following a persistent infection with high-risk human papillomavirus (hrHPV) is driven by additional host-cell changes, such as altered DNA methylation. In previous studies, we have identified 12 methylated host genes associated with cervical cancer and pre-cancer (CIN2/3). This study systematically analyzed the onset and DNA methylation pattern of these genes during hrHPV-induced carcinogenesis using a longitudinal in vitro model of hrHPV-transformed cell lines (n = 14) and hrHPV-positive cervical scrapings (n = 113) covering various stages of cervical carcinogenesis.
View Article and Find Full Text PDFBackground: High-grade anal intraepithelial neoplasia (AIN2/3; HGAIN) is highly prevalent in human immunodeficiency virus positive (HIV+) men who have sex with men (MSM), but only a minority will eventually progress to cancer. Currently, the cancer risk cannot be established, and therefore all HGAIN is treated, resulting in overtreatment. We assessed host cell deoxyribonucleic acid (DNA) methylation markers for detecting HGAIN and anal cancer.
View Article and Find Full Text PDFBackground: Primary testing for high-risk HPV (hrHPV) is increasingly implemented in cervical cancer screening programs. Many hrHPV-positive women, however, harbor clinically irrelevant infections, demanding additional disease markers to prevent over-referral and over-treatment. Most promising biomarkers reflect molecular events relevant to the disease process that can be measured objectively in small amounts of clinical material, such as miRNAs.
View Article and Find Full Text PDFOffering self-sampling of cervico-vaginal material for high-risk human papillomavirus (hrHPV) testing is an effective method to increase the coverage in cervical screening programs. Molecular triage directly on hrHPV-positive self-samples for colposcopy referral opens the way to full molecular cervical screening. Here, we set out to identify a DNA methylation classifier for detection of cervical precancer (CIN3) and cancer, applicable to lavage and brush self-samples.
View Article and Find Full Text PDFBackground: Aggregating gene expression data across experiments via meta-analysis is expected to increase the precision of the effect estimates and to increase the statistical power to detect a certain fold change. This study evaluates the potential benefit of using a meta-analysis approach as a gene selection method prior to predictive modeling in gene expression data.
Results: Six raw datasets from different gene expression experiments in acute myeloid leukemia (AML) and 11 different classification methods were used to build classification models to classify samples as either AML or healthy control.
Epigenetic host cell changes involved in cervical cancer development following a persistent high-risk human papillomavirus (hrHPV) infection, provide promising markers for the management of hrHPV-positive women. In particular, markers based on DNA methylation of tumor suppressor gene promoters are valuable. These markers ideally identify hrHPV-positive women with precancer (CIN2/3) in need of treatment.
View Article and Find Full Text PDFSummary: Our aim is to improve omics based prediction and feature selection using multiple sources of auxiliary information: co-data. Adaptive group regularized ridge regression (GRridge) was proposed to achieve this by estimating additional group-based penalty parameters through an empirical Bayes method at a low computational cost. We illustrate the GRridge method and software on RNA sequencing datasets.
View Article and Find Full Text PDFMotivation: Class predicting with gene expression is widely used to generate diagnostic and/or prognostic models. The literature reveals that classification functions perform differently across gene expression datasets. The question, which classification function should be used for a given dataset remains to be answered.
View Article and Find Full Text PDFMost of the discoveries from gene expression data are driven by a study claiming an optimal subset of genes that play a key role in a specific disease. Meta-analysis of the available datasets can help in getting concordant results so that a real-life application may be more successful. Sequential meta-analysis (SMA) is an approach for combining studies in chronological order while preserving the type I error and pre-specifying the statistical power to detect a given effect size.
View Article and Find Full Text PDFBackground: Class prediction models have been shown to have varying performances in clinical gene expression datasets. Previous evaluation studies, mostly done in the field of cancer, showed that the accuracy of class prediction models differs from dataset to dataset and depends on the type of classification function. While a substantial amount of information is known about the characteristics of classification functions, little has been done to determine which characteristics of gene expression data have impact on the performance of a classifier.
View Article and Find Full Text PDFThe literature shows that classifiers perform differently across datasets and that correlations within datasets affect the performance of classifiers. The question that arises is whether the correlation structure within datasets differ significantly across diseases. In this study, we evaluated the homogeneity of correlation structures within and between datasets of six etiological disease categories; inflammatory, immune, infectious, degenerative, hereditary and acute myeloid leukemia (AML).
View Article and Find Full Text PDFClassification methods used in microarray studies for gene expression are diverse in the way they deal with the underlying complexity of the data, as well as in the technique used to build the classification model. The MAQC II study on cancer classification problems has found that performance was affected by factors such as the classification algorithm, cross validation method, number of genes, and gene selection method. In this paper, we study the hypothesis that the disease under study significantly determines which method is optimal, and that additionally sample size, class imbalance, type of medical question (diagnostic, prognostic or treatment response), and microarray platform are potentially influential.
View Article and Find Full Text PDFContemp Clin Trials
January 2014
Estimators for the variance between treatment effects from randomized clinical trials (RCTs) in a meta-analysis may yield divergent or even contradictory results. In a sequential meta-analysis (SMA), their properties are even more important, as they influence the point in time at which definite conclusions are drawn. In this study, we evaluated the properties of estimators of heterogeneity to be used in an SMA.
View Article and Find Full Text PDFBackground: By means of optical coherence tomography (OCT), coronary dimensions can be assessed accurately. However, whether OCT can identify hemodynamic significant coronary lesions as determined by fractional flow reserve (FFR) in patients with an in-stent lesion is not known. Therefore, we tried to assess the predictive value of OCT parameters in this setting as compared to FFR.
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