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
20P - Effects of <italic>Apis dorsata</italic> honey on the expression of selected CYP450, pro-apoptotic, and anti-apoptotic genes during induced cytotoxicity in cyclophosphamide-treated human lung carcinoma (A549) cells
Presenter: Jose Kenneth Narag
Session: Cocktail & Poster Display session
Resources:
Abstract
21P - Hsa_circ_0009061 inhibits the progression of bladder cancer through the miR-889-3p/CPEB3 axis
Presenter: Minkang Wu
Session: Cocktail & Poster Display session
Resources:
Abstract
22P - Exploring exportin-1 as a therapeutic vulnerability in lung squamous cell carcinoma
Presenter: Vidushi Durani
Session: Cocktail & Poster Display session
Resources:
Abstract
23P - Identification of HPSE as potential novel therapeutic target for lung adenocarcinoma patients
Presenter: Samuel Doré
Session: Cocktail & Poster Display session
Resources:
Abstract
24P - High-throughput plasma proteomics profiling in early breast cancer
Presenter: Isabella Lombardo
Session: Cocktail & Poster Display session
Resources:
Abstract
25P - Immunohistochemical analysis of ROR1 and BMI-1 expression in luminal breast cancer
Presenter: Sergey Vtorushin
Session: Cocktail & Poster Display session
Resources:
Abstract
26P - Associations between cancer stem cells (CSC) markers and androgen (AR) and estrogen (ER) receptors expression in prostate cancer (PCa)
Presenter: Marina Puchinskaya
Session: Cocktail & Poster Display session
Resources:
Abstract
27P - Proteomic profiling reveals organ-specific differences in metastases and identifies potential biomarkers for recurrence risk in localized colon cancer
Presenter: Blanca García-Micó
Session: Cocktail & Poster Display session
Resources:
Abstract
28P - Collagen-activated signalling pathway is significantly hypermethylated in high-grade serous ovarian cancer (HGSOC) patients treated with platinum-containing neoadjuvant chemotherapy (NACT)
Presenter: Jose Alejandro Perez Fidalgo
Session: Cocktail & Poster Display session
Resources:
Abstract
29P - Quantitative tissue analysis reveal adenylate kinase 2 protein signatures: Therapeutic target for meningioma
Presenter: Rashmi Rana
Session: Cocktail & Poster Display session
Resources:
Abstract