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
41P - HLA genotypes modify the age-related penetrance of BRCA1 pathogenic variants in breast cancer patients
Presenter: Ekaterina Kuligina
Session: Cocktail & Poster Display session
Resources:
Abstract
42P - Investigating the influence of extrachromosomal DNA in the progression of non-small cell lung cancer through the TRACERx and PEACE studies
Presenter: Jeanette Kittel
Session: Cocktail & Poster Display session
Resources:
Abstract
43P - MDM2 alterations in primary brain tumors: A potential niche for targeted therapy
Presenter: Diego Gomez Puerto
Session: Cocktail & Poster Display session
Resources:
Abstract
44P - Exploring miR-205 and miR-296 as salivary biomarkers and potential therapeutic targets in oral cancer
Presenter: Thaís Moré Milan
Session: Cocktail & Poster Display session
Resources:
Abstract
46P - The role of microRNA-1246 in early detection of breast cancer: Findings from a systematic review and meta-analysis
Presenter: Muhammed Elfaituri
Session: Cocktail & Poster Display session
Resources:
Abstract
47P - Differential expression of discriminative markers in matched invasion fronts and tumour buds in CRC
Presenter: Laura Grech
Session: Cocktail & Poster Display session
Resources:
Abstract
48P - Transcriptome profiling highlights distinct gene signatures in HER2 high (HER2 3+) and HER 2 low (Her2 1+/2+) breast cancers
Presenter: Tamanna Thakur
Session: Cocktail & Poster Display session
Resources:
Abstract
49P - MiR-155 promotes breast cancer progression by upregulating cancer stemness
Presenter: Jeonghee Han
Session: Cocktail & Poster Display session
Resources:
Abstract
50P - Clinical impact of actionable molecular variants disclosed in late-stage cancer patients by tumor whole-exome sequencing in a prospective single-institution study
Presenter: Christophe Mapendano
Session: Cocktail & Poster Display session
Resources:
Abstract
51P - Functional characterization of the novel long intergenic non-coding RNA-RFC4, a transcript regulating chromosomal instability in prostate cancer
Presenter: Rogelio Montiel Manríquez
Session: Cocktail & Poster Display session
Resources:
Abstract