Publications by authors named "Martin Widschwendter"
The burden of uterine cancer is growing and, in the US and UK, mortality rates are poorest among black women. Early detection of these cancers is critical and poor performance of ultrasound in black women may contribute to adverse outcomes. Limited data on this topic are available from Africa.
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- The study examines the reliability of the Illumina Methylation array platform in measuring DNA methylation by evaluating the consistency of repeated measures using both type I and type II Infinium probes.
- A new method is proposed to identify unreliable probes by using dynamic thresholds for mean intensity (MI) and unreliability scores based on simulations that factor in technical noise.
- Validation across multiple datasets indicates that probes with low MI tend to show higher variability in β values, and an R package is introduced to help researchers calculate MI and unreliability scores for better data analysis.
Article Synopsis
- Biomarkers of aging (BOA) are special measurements that can help scientists understand how old someone is on a biological level and how this changes with treatments.
- Recently, many new BOA have been discovered that could really help people live healthier lives as they age, but there are some problems getting these ideas into actual medical practice.
- Experts found six main challenges that are stopping BOA from being used more widely and suggested ways to make them better, such as ensuring they are easy to access and useful for everyone.
Article Synopsis
- Mifepristone (MIF) is a synthetic hormone used for pharmacological abortions and treating certain medical conditions, and the study aimed to create a reliable method to measure MIF and its metabolite (MET) in plasma and tissue samples from mice.
- The researchers developed a high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) method that efficiently extracts and quantifies these substances, with quick run times and high sensitivity.
- The method demonstrated effective separation and detection limits that could potentially be adapted for human medical research.
Purpose: The purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC).
Experimental Design: RB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1,134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes, and transcriptomic subtypes.
Cervical cancer (CC) screening in women comprises human papillomavirus (HPV) testing followed by cytology triage of positive cases. Drawbacks, including cytology's low reproducibility and requirement for short screening intervals, raise the need for alternative triage methods. Here we used an innovative triage technique, the WID-qCIN test, to assess the DNA methylation of human genes DPP6, RALYL and GSX1 in a real-life cohort of 28,017 women aged ≥30 years who attended CC screening in Stockholm between January and March 2017.
View Article and Find Full Text PDFEndometrial cancer (EC) is the most prevalent gynaecological cancer in high-income countries and its incidence is continuing to rise sharply. Simple and objective tools to reliably detect women with EC are urgently needed. We recently developed and validated the DNA methylation (DNAme)-based women's cancer risk identification-quantitative polymerase chain reaction test for endometrial cancer (WID-qEC) test that could address this need.
View Article and Find Full Text PDFBackground: To evaluate outcomes of laparoscopic retroperitoneal para-aortic lymphadenectomy for stage 1b3-3b cervical cancer.
Methods: Pathology databases searched for all para-aortic lymphadenectomy cases 2005-2016. Descriptive statistics were used to analyse baseline characteristics, cox models for treatment affect after accounting for variables, and Kaplan Meier curves for survival (STATA v15).
Background: Approximately 40% of all recorded deaths in Austria are due to behavioral risks. These risks could be avoided with appropriate measures.
Objectives: Extension of the concept of EHR and EMR to an electronic prevention record, focusing on primary and secondary prevention.
Background: Tissue-specificity for fimbrial fallopian tube ovarian carcinogenesis remains largely unknown in mutation carriers. We aimed to assess the cell autonomous and cell-nonautonomous implications of a germline mutation in the context of cancer immunosurveillance of CD3 CD56 natural killer (NK) cells.
Methods: Premenopausal mutation carriers versus age-matched non-carriers were compared.
Unlabelled: Tobacco use is a major modifiable risk factor for adverse health outcomes, including cancer, and elicits profound epigenetic changes thought to be associated with long-term cancer risk. While electronic cigarettes (e-cigarettes) have been advocated as harm reduction alternatives to tobacco products, recent studies have revealed potential detrimental effects, highlighting the urgent need for further research into the molecular and health impacts of e-cigarettes. Here, we applied computational deconvolution methods to dissect the cell- and tissue-specific epigenetic effects of tobacco or e-cigarette use on DNA methylation (DNAme) in over 3,500 buccal/saliva, cervical, or blood samples, spanning epithelial and immune cells at directly and indirectly exposed sites.
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- The search for biomarkers that measure biological aging, especially 'omic'-based ones, has gained momentum, aiming to predict aging outcomes and assess interventions for healthy aging.
- There is currently no agreement on the best methods to validate these aging biomarkers before using them in clinical settings.
- The review emphasizes the need for systematic validation, which can enhance the reliability and effectiveness of aging biomarkers in clinical research and trials focused on longevity.
Article Synopsis
- Researchers studied a common genetic change that happens in a type of ovarian cancer called high-grade serous carcinoma (HGSC), looking at how it affects patient survival.
- They found that losing the RB1 protein was linked to longer survival in patients with HGSC, but it was the opposite for a different type of ovarian cancer called endometrioid cancer.
- Patients with both RB1 loss and certain inherited genetic changes had much better survival rates compared to those with just one of these problems or none at all.
Article Synopsis
- Researchers are investigating the effectiveness of a new DNA methylation test (WID-qEC) compared to traditional imaging tests for detecting uterine cancer in women experiencing abnormal uterine bleeding.
- The study, called EPI-SURE, involved women aged 45 and older attending a gynecological diagnostic center and collected cervicovaginal samples alongside standard imaging tests.
- Out of 474 potential participants, 399 women were included for analysis, and initial findings highlighted that approximately 47% received recommendations for further examination based on the imaging tests.
Analysis of cell-free DNA methylation (cfDNAme), alone or combined with CA125, could help to detect ovarian cancers earlier and may reduce mortality. We assessed cfDNAme in regions of ZNF154, C2CD4D and WNT6 via targeted bisulfite sequencing in diagnostic and early detection (preceding diagnosis) settings. Diagnostic samples were obtained via prospective blood collection in cell-free DNA tubes in a convenience series of patients with a pelvic mass.
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- Researchers developed a new index called WID™-qtBC that uses DNA methylation levels to help identify women at risk for breast cancer, going beyond traditional genetic assessments.
- The study showed that women with a combination of high polygenic risk scores and elevated WID™-qtBC levels have a significantly increased risk (9.6 times) for developing breast cancer.
- The WID™-qtBC can be influenced by lifestyle factors like age and body mass index, and may be modifiable through preventive treatments, highlighting the interaction between genetics and environmental factors in cancer risk.
Article Synopsis
- The growth of aging biology research is focusing on finding and assessing longevity interventions for humans, making biomarkers of aging essential tools for these efforts.
- A lack of standards and consensus on what makes a reliable aging biomarker currently limits their development and application in clinical settings.
- The article proposes a framework for categorizing aging biomarkers, discussing validation processes, and identifying challenges that need future research to facilitate their use in clinical trials and practices.
Article Synopsis
- The study aimed to investigate the relationship between p53 protein expression and survival rates in women with different types of ovarian cancer, particularly high-grade serous carcinoma (HGSC), endometrioid carcinoma (EC), and clear cell carcinoma (CCC), using a large cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium.
- It was found that abnormal p53 expression patterns were prevalent in 93.4% of HGSC cases, but in EC and CCC, these abnormal patterns were linked to a significantly higher risk of death, indicating a poor prognosis.
- The research concluded that while abnormal p53 expression doesn't affect survival in HGSC, it serves as a strong independent prognostic marker for EC and CCC,
The impact of a pathogen on host disease can only be studied in samples covering the entire spectrum of pathogenesis. Persistent oncogenic human papilloma virus (HPV) infection is the most common cause for cervical cancer. Here, we investigate HPV-induced host epigenome-wide changes prior to development of cytological abnormalities.
View Article and Find Full Text PDFBackground: Better understanding of prognostic factors in tubo-ovarian high-grade serous carcinoma (HGSC) is critical, as diagnosis confers an aggressive disease course. Variation in tumor DNA methylation shows promise predicting outcome, yet prior studies were largely platform-specific and unable to evaluate multiple molecular features.
Methods: We analyzed genome-wide DNA methylation in 1,040 frozen HGSC, including 325 previously reported upon, seeking a multi-platform quantitative methylation signature that we evaluated in relation to clinical features, tumor characteristics, time to recurrence/death, extent of CD8+ tumor-infiltrating lymphocytes (TIL), gene expression molecular subtypes, and gene expression of the ATP-binding cassette transporter TAP1.
The incidence of endometrial cancer is rising. Measures to identify women at risk and to detect endometrial cancer earlier are required to reduce the morbidity triggered by the aggressive treatment required for advanced endometrial cancer. We developed the WID-EC (Women's cancer risk IDentification-Endometrial Cancer) test, which is based on DNA methylation at 500 CpG sites, in a discovery set of cervical liquid-based cytology samples from 1086 women with and without an endometrial cancer (217 cancer cases and 869 healthy controls) with a worse prognosis (grade 3 or ≥stage IB).
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- - Cervical screening with HPV testing and cytology is being adopted globally, but cytology has limitations, particularly in younger women; this study aimed to create a reliable triage test called WID™-qCIN that efficiently predicts progression to CIN3+ in HPV-positive patients.
- - The WID™-qCIN test, analyzing specific human gene regions, showed impressive results: 100% sensitivity for invasive cancer detection and 78% for CIN3, with a specificity of 90%, effectively identifying at-risk women, especially those with initially negative cytology.
- - The study concludes that WID™-qCIN represents a significant advancement over traditional cervical screening methods, suggesting it could provide an affordable and
Article Synopsis
- Mucinous ovarian carcinoma (MOC) is a rare type of ovarian cancer that doesn’t respond well to regular chemotherapy and has poor survival rates for advanced cases.
- Researchers studied tissue samples from 126 MOC patients to understand the types of immune cells in the tumors.
- Most MOCs have very few immune cells ("cold" tumors), which suggests these patients might not respond well to immune therapies.
Article Synopsis
- Cervical screening is shifting from using cytology to primarily testing for high-risk HPV, but there's a need for a specific test to identify which HPV-positive women require further investigation for serious cervical conditions like CIN3+.
- Researchers analyzed DNA methylation patterns across thousands of samples to develop a new test called WID-CIN, which successfully identifies higher-risk cases of CIN3+ with impressive sensitivity and specificity.
- The WID-CIN test demonstrated a 92.7% sensitivity in women over 30, making it a promising tool for better triaging patients and potentially improving cervical cancer screenings.