scholarly journals Hypermethylated PCDHGB7 as a Biomarker for Early Detection of Endometrial Cancer in Endometrial Brush Samples and Cervical Scrapings

2022 ◽  
Vol 8 ◽  
Author(s):  
Jiangjing Yuan ◽  
Zhanrui Mao ◽  
Qi Lu ◽  
Peng Xu ◽  
Chengyang Wang ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Early Detection ◽  
Minimally Invasive ◽  
Predictive Value ◽  
Developed Countries ◽  
The Cancer Genome Atlas ◽  
Clinical Samples ◽  
Data Sets ◽  
Methylation Marker ◽  
Validation Set

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.

scholarly journals Metabolomic Biomarkers for the Detection of Obesity-Driven Endometrial Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 718
Author(s):  
Kelechi Njoku ◽  
Amy E. Campbell ◽  
Bethany Geary ◽  
Michelle L. MacKintosh ◽  
Abigail E. Derbyshire ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Early Detection ◽  
Minimally Invasive ◽  
Cancer Detection ◽  
Test Performance ◽  
Female Genital Tract ◽  
Screening Tools ◽  
Normal Endometrium ◽  
Endometrioid Endometrial Cancer ◽  
Post Menopausal

Endometrial cancer is the most common malignancy of the female genital tract and a major cause of morbidity and mortality in women. Early detection is key to ensuring good outcomes but a lack of minimally invasive screening tools is a significant barrier. Most endometrial cancers are obesity-driven and develop in the context of severe metabolomic dysfunction. Blood-derived metabolites may therefore provide clinically relevant biomarkers for endometrial cancer detection. In this study, we analysed plasma samples of women with body mass index (BMI) ≥ 30 kg/m2 and endometrioid endometrial cancer (cases, n = 67) or histologically normal endometrium (controls, n = 69), using a mass spectrometry-based metabolomics approach. Eighty percent of the samples were randomly selected to serve as a training set and the remaining 20% were used to qualify test performance. Robust predictive models (AUC > 0.9) for endometrial cancer detection based on artificial intelligence algorithms were developed and validated. Phospholipids were of significance as biomarkers of endometrial cancer, with sphingolipids (sphingomyelins) discriminatory in post-menopausal women. An algorithm combining the top ten performing metabolites showed 92.6% prediction accuracy (AUC of 0.95) for endometrial cancer detection. These results suggest that a simple blood test could enable the early detection of endometrial cancer and provide the basis for a minimally invasive screening tool for women with a BMI ≥ 30 kg/m2.

scholarly journals Controversies in the Management of Endometrial Carcinoma: An Update

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Mohamed K. Mehasseb ◽  
John A. Latimer
Keyword(s):  
Radiation Therapy ◽  
Endometrial Cancer ◽  
Early Detection ◽  
Endometrial Carcinoma ◽  
Genital Tract ◽  
Female Genital Tract ◽  
Developed Countries ◽  
Changing Roles ◽  
The Developed Countries ◽  
Female Genital

Endometrial carcinoma is the commonest type of female genital tract malignancy in the developed countries. Endometrial carcinoma is usually confined to the uterus at the time of diagnosis and as such usually carries an excellent prognosis with high curability. Our understanding and management of endometrial cancer have continuously developed. Current controversies focus on screening and early detection, the extent of nodal surgery, and the changing roles of radiation therapy and chemotherapy and will be discussed in this paper.

scholarly journals Prognostic classification of endometrial cancer using a molecular approach based on a twelve-gene NGS panel

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Raquel López-Reig ◽  
Antonio Fernández-Serra ◽  
Ignacio Romero ◽  
Cristina Zorrero ◽  
Carmen Illueca ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Copy Number ◽  
Disease Free Survival ◽  
Developed Countries ◽  
Molecular Techniques ◽  
The Cancer Genome Atlas ◽  
Molecular Approach ◽  
Random Forest Classification ◽  
Forest Classification ◽  
Prognostic Groups

AbstractEndometrial Cancer (EC) is one of the most common malignancies in women in developed countries. Molecular characterization of different biotypes may improve clinical management of EC. The Cancer Genome Atlas (TCGA) project has revealed four prognostic EC subgroups: POLE, MSI; Copy Number Low (CNL) and Copy Number High (CNH). The goal of this study was to develop a method to classify tumors in any of the four EC prognostic groups using affordable molecular techniques. Ninety-six Formalin-Fixed Paraffin-embedded (FFPE) samples were sequenced following a NGS TruSeq Custom Amplicon low input (Illumina) protocol interrogating a multi-gene panel. MSI analysis was performed by fragment analysis using eight specific microsatellite markers. A Random Forest classification algorithm (RFA), considering NGS results, was developed to stratify EC patients into different prognostic groups. Our approach correctly classifies the EC patients into the four TCGA prognostic biotypes. The RFA assigned the samples to the CNH and CNL groups with an accuracy of 0.9753 (p < 0.001). The prognostic value of these groups was prospectively reproduced on our series both for Disease-Free Survival (p = 0.004) and Overall Survival (p = 0.030).Hence, with the molecular approach herein described, a precise and suitable tool that mimics the prognostic EC subtypes has been solved and validated. Procedure that might be introduced into routine diagnostic practices.

scholarly journals Possible Human Papillomavirus 38 Contamination of Endometrial Cancer RNA Sequencing Samples in The Cancer Genome Atlas Database

2015 ◽  
Vol 89 (17) ◽  
pp. 8967-8973 ◽  
Author(s):  
Majid Kazemian ◽  
Min Ren ◽  
Jian-Xin Lin ◽  
Wei Liao ◽  
Rosanne Spolski ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Human Papillomavirus ◽  
Rna Sequencing ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Clinical Samples ◽  
Cross Contamination ◽  
Rna Seq ◽  
Cancer Genome Atlas ◽  
Genome Atlas

ABSTRACTViruses are causally associated with a number of human malignancies. In this study, we sought to identify new virus-cancer associations by searching RNA sequencing data sets from >2,000 patients, encompassing 21 cancers from The Cancer Genome Atlas (TCGA), for the presence of viral sequences. In agreement with previous studies, we found human papillomavirus 16 (HPV16) and HPV18 in oropharyngeal cancer and hepatitis B and C viruses in liver cancer. Unexpectedly, however, we found HPV38, a cutaneous form of HPV associated with skin cancer, in 32 of 168 samples from endometrial cancer. In 12 of the HPV38-positive (HPV38+) samples, we observed at least one paired read that mapped to both human and HPV38 genomes, indicative of viral integration into the host DNA, something not previously demonstrated for HPV38. The expression levels of HPV38 transcripts were relatively low, and all 32 HPV38+samples belonged to the same experimental batch of 40 samples, whereas none of the other 128 endometrial carcinoma samples were HPV38+, raising doubts about the significance of the HPV38 association. Moreover, the HPV38+samples contained the same 10 novel single nucleotide variations (SNVs), leading us to hypothesize that one patient was infected with this new isolate of HPV38, which was integrated into his/her genome and may have cross-contaminated other TCGA samples within batch 228. Based on our analysis, we propose guidelines to examine the batch effect, virus expression level, and SNVs as part of next-generation sequencing (NGS) data analysis for evaluating the significance of viral/pathogen sequences in clinical samples.IMPORTANCEHigh-throughput RNA sequencing (RNA-Seq), followed by computational analysis, has vastly accelerated the identification of viral and other pathogenic sequences in clinical samples, but cross-contamination during the processing of the samples remain a major problem that can lead to erroneous conclusions. We found HPV38 sequences specifically present in RNA-Seq samples from endometrial cancer patients from TCGA, a virus not previously associated with this type of cancer. However, multiple lines of evidence suggest possible cross-contamination in these samples, which were processed together in the same batch. Despite this potential cross-contamination, our data indicate that we have detected a new isolate of HPV38 that appears to be integrated into the human genome. We also provide general guidelines for computational detection and interpretation of pathogen-disease associations.

scholarly journals An miRNA signature associated with tumor mutation burden in endometrial cancer

2020 ◽  
Vol 40 (11) ◽  
Author(s):  
Hongyu Zhou ◽  
Lihua Chen ◽  
Mei Qin ◽  
Yajie Lei ◽  
Tianjiao Li ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
The Cancer Genome Atlas ◽  
Immune Checkpoints ◽  
Mirna Signature ◽  
Training Set ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Validation Set ◽  
Brca1 Brca2 ◽  
Selection Operator

Abstract Tumor mutation burden (TMB) is an essential biomarker to predict immunotherapy response. TMB measurement was mainly evaluated by whole-exome sequencing (WES), which was costly and difficult to be widely applied. In the present study, we aimed to establish and validate a miRNA signature to predict TMB level in endometrial cancer using The Cancer Genome Atlas (TCGA) database. MiRNA expression and somatic mutation profiles of uterine corpus endometrial carcinoma (UCEC) were downloaded from TCGA database. Total 518 patients with UCEC were randomly classified into training set (n=311) and validation set (n=207). Thirty-five differentially expressed miRNAs between high-TMB and low-TMB group were identified in training set. Least absolute shrinkage and selection operator (LASSO) method was performed to select out 26 miRNAs to establish the optimal signature. The accuracy of the miRNA signature for predicting TMB level was 0.833 for training set, 0.749 for validation set and 0.799 for total set. Moreover, the miRNA signature had significant correlation with immune checkpoints related genes (PD-1, PD-L1, CTLA-4) and mismatch repair related genes (BRCA1, BRCA2, MLH1, MSH6) expression. In conclusion, this miRNA signature could predict TMB level in endometrial cancer and might have some merits in providing guidance for immunotherapy in endometrial cancer.

scholarly journals Identification of DNA methylation markers for early detection of CRC indicates a role for nervous system-related genes in CRC

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Glenn Rademakers ◽  
Maartje Massen ◽  
Alexander Koch ◽  
Muriel X. Draht ◽  
Nikkie Buekers ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Nervous System ◽  
Gene Ontology ◽  
Early Detection ◽  
Colon Adenocarcinoma ◽  
The Cancer Genome Atlas ◽  
Data Set ◽  
Methylation Marker ◽  
Diagnostic Potential ◽  
Gene Ontology Enrichment

Abstract Purpose Colonoscopy and the fecal immunochemical test (FIT) are currently the most widely used screening modalities for colorectal cancer (CRC), however, both with their own limitations. Here we aim to identify and validate stool-based DNA methylation markers for the early detection of CRC and investigate the biological pathways prone to DNA methylation. Methods DNA methylation marker discovery was performed using The Cancer Genome Atlas (TCGA) colon adenocarcinoma data set consisting of normal and primary colon adenocarcinoma tissue. The performance of the five best candidate markers and a previously identified marker, NDRG4, was evaluated on tissues and whole stool samples of healthy subjects and CRC patients using quantitative MSP assays. The results were compared and combined with FIT data. Finally, pathway and gene ontology enrichment analyses were performed using ToppFun, GOrilla and clusterProfiler. Results GDNF, HAND2, SLC35F3, SNAP91 and SORCS1 were ranked as the best performing markers. Gene combinations of all five markers, NDRG4 and FIT were evaluated to establish the biomarker panel with the highest diagnostic potential, resulting in the identification of GDNF/SNAP91/NDRG4/FIT as the best performing marker panel. Pathway and gene ontology enrichment analyses revealed that genes associated with the nervous system were enriched in the set of best performing CRC-specific biomarkers. Conclusion In silico discovery analysis using TCGA-derived data yielded a novel DNA-methylation-based assay for the early detection of CRC, potentially improving current screening modalities. Additionally, nervous system-related pathways were enriched in the identified genes, indicating an epigenetic regulation of neuronal genes in CRC.

Sarginio limfmazgio nustatymas sergant endometriumo vėžiu: nauja chirurginio stadijavimo kryptis

2020 ◽  
Vol 23 (1) ◽  
Author(s):  
Linas Andreika ◽  
Margarita Montrimaitė ◽  
Juliana Andreičik
Keyword(s):  
Endometrial Cancer ◽  
Lymph Node ◽  
Sentinel Lymph Node ◽  
Sentinel Lymph Node Biopsy ◽  
Gynecological Cancer ◽  
Developed Countries ◽  
Lymph Node Biopsy ◽  
Sentinel Lymph Nodes ◽  
Cancer Management ◽  
Node Biopsy

Summary. Endometrial cancer is the most common gynecological cancer in developed countries. Biopsy of the sentinel lymph node can be considered as an alternative to full lymphadenectomy. In order to identify sentinel lymph nodes, a tracer substance is injected into the uterus to visualize the lymphatic tract. Commonly used tracer substances are Technetium-99m (99mTc) colloid, blue dyes, and indocyanine green (ICG). In this review the significance of sentinel lymph node biopsy in endometrial cancer management and the technique of the procedure is discussed.

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