Abstract 45P
Background
Although 4 molecular subtypes of endometrial cancer (EC) by The Cancer Genome Atlas (TGGA) have distinctive prognostic features, prognosis within each subtype could vary depending on histological and molecular factors. By merging omics datasets and machine learning analyses, we attempted to identify biomarkers related to the recurrence within each molecular subtype.
Methods
From TCGA multi-omics datasets, 116 EC samples with DNA methylation, RNA-seq, and common variants as well as recurrence data were used for analysis. Differentially expressed genes (DEGs) and differentially methylated regions (DMRs) were retrieved by t-test between the recurrence and non-recurrence groups. DEGs and DMRs were visualized using volcano plots and heat maps. The machine learning approaches, namely decision tree (DT) and random forest (RF) models, were used to find the molecular factors to best discriminate the following 4 groups: copy number-high (CN-H) with recurrence, CN-H without recurrence, copy number-low (CN-L) with recurrence, and CN-L without recurrence. Critical gene expressions or DNA methylation levels in each molecular subtypes were presented as a boxplot.
Results
Three omics datasets were merged with 378,278 CpG sites, 53,409 normalized gene expression levels, 118,555 genomic region variants, and 18,603 gene variants. Through DT and RF, PARD6G-AS1, CSMD1, TESC, and CD44 were selected. Boxplot revealed that hypomethylation of PARD6G-AS1, hypermethylation of CSMD1, and increased TESC expression were significantly associated with increased risk of recurrence in the CN-H group. Also, overexpression of CD44 was significantly associated with recurrence in the CN-L group. After validation of these 4 parameters using TCGA raw data, PARD6G-AS1 and CD44 remained their statistical significance (P=0.006 and 0.020, respectively). Hypomethylation of PARD6G-AS1 in CN-H and CD44 overexpression in CN-L demonstrated significant association with both advanced stage and lymph node metastasis.
Conclusions
Hypomethylation of PARD6G-AS1 in CN-H and CD44 overexpression in CN-L could be predictive markers in endometrial cancer recurrence.
Editorial acknowledgement
Clinical trial identification
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
104P - Hypomethylated immune gene promoters as potential biomarkers in oral and oropharyngeal cancer
Presenter: Petra Anić
Session: Cocktail & Poster Display session
Resources:
Abstract
105P - Implementation of technical improvements in cfMeDIP-Seq library preparation
Presenter: Martina Dameri
Session: Cocktail & Poster Display session
Resources:
Abstract
106P - Clinical application of next-generation sequencing in metastatic colorectal cancer (mCRC): Experience from a comprehensive cancer centre
Presenter: David Lluís Garulo
Session: Cocktail & Poster Display session
Resources:
Abstract
107P - Unveiling mismatch repair deficiency (dMMR) and microsatellite-instability high (MSI-H) detection in cancer patients (pt) using a next-generation sequencing (NGS)-based molecular pre-screening program (MPP)
Presenter: Lucia Notario Rincon
Session: Cocktail & Poster Display session
Resources:
Abstract
108P - Validation and implementation of a large NGS panel to test liquid biopsies from patients with suspected advanced non-small cell lung cancer (NSCLC) in an NHS genomic laboratory for the QuicDNA biomarker study
Presenter: Rachel Dodds
Session: Cocktail & Poster Display session
Resources:
Abstract
109P - A multiomic, single-cell measurable residual disease (scMRD) assay for phasing DNA mutations and surface immunophenotypes
Presenter: Simone Formisano
Session: Cocktail & Poster Display session
Resources:
Abstract
110P - Multicellular three-dimensional tumor spheroid of nasopharyngeal carcinoma
Presenter: Shiau Chuen Cheah
Session: Cocktail & Poster Display session
Resources:
Abstract
111P - Development of digital PCR for accurate measurement of HER2 amplification in 184 gastric cancer patients
Presenter: So Young Kang
Session: Cocktail & Poster Display session
Resources:
Abstract
112P - A novel methylation-sensitive assay for early detection of hepatocellular carcinoma to improve surveillance
Presenter: Jeong Sil Ha
Session: Cocktail & Poster Display session
Resources:
Abstract
113P - Evaluation of effects of tissue preservation methods on the proteome abundance through deep proteomics of breast cancer tissue
Presenter: Shashwati parihari
Session: Cocktail & Poster Display session
Resources:
Abstract