ArticleFrontiers in genetics2020
Identification of Prognostic Markers in Cholangiocarcinoma Using Altered DNA Methylation and Gene Expression Profiles.
Article in Frontiers in genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 17 citations in OpenAlex.
- Advances in the Molecular Mechanisms of Cholangiocarcinoma: A Comprehensive Review of Biomarkers, Regulatory Pathways and Tumor Microenvironment Reprogramming.International journal of molecular sciences · 2026Review
- PIWIL4: from biological characteristics to disease pathogenesis and clinical applications.Frontiers in oncology · 2026Review
- Validation of Prognostic Circulating Cell-Free RNA BiomarkersCurrent issues in molecular biology · 2025Article
- Whole Transcriptome Sequencing Analyzes the Interactions of mRNAs and ncRNAs in Cholangiocarcinoma.Cancer medicine · 2025Article
- Aberrant ALPP Expression Serves as a Prognostic Biomarker and Facilitates Cholangiocarcinoma Progression through Immune Evasion and PI3K-Akt Signaling Activation.International journal of medical sciences · 2025Article
- Novel Insights into PGM2L1 as a Prognostic Biomarker in Cholangiocarcinoma: Implications for Metabolic Reprogramming and Tumor Microenvironment Modulation.International journal of medical sciences · 2025Article
- GAIN-BRCA: a graph-based AI-net framework for breast cancer subtype classification using multiomics data.Bioinformatics advances · 2025Article
- Roles of DEPDC1 in various types of cancer (Review).Oncology letters · 2024Review
- Integration analysis of miRNA-mRNA expression exploring their potential roles in intrahepatic cholangiocarcinoma.Scientific reports · 2023Article
- DEPDC1 and KIF4A synergistically inhibit the malignant biological behavior of osteosarcoma cells through Hippo signaling pathway.Journal of orthopaedic surgery and research · 2023Article
- Advances in prognostic and therapeutic targets for hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The hippo signaling pathway.Frontiers in oncology · 2022Review
- PIWIL4 and SUPT5H combine to predict prognosis and immune landscape in intrahepatic cholangiocarcinoma.Cancer cell international · 2021Article
- The Role of microRNAs in Cholangiocarcinoma.International journal of molecular sciences · 2021Review
- Review
- Article
- Aberrantly DNA Methylated-Differentially Expressed Genes in Pancreatic Cancer Through an Integrated Bioinformatics Approach.Frontiers in genetics · 2021Article
- The Use of Machine Learning to Create a Risk Score to Predict Survival in Patients with Hepatocellular Carcinoma: A TCGA Cohort Analysis.Canadian journal of gastroenterology & hepatology · 2021Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCholangiocarcinoma (CCA) is a rare disease, but it is amongst the most lethal cancers with a median survival under 1 year. Variations in DNA methylation and gene expression have been extensively studied in other cancers for their role in pathogenesis and disease prognosis, but these studies are very limited in CCA. This study focusses on the identification of DNA methylation and gene expression prognostic biomarkers using multi-omics data of CCA tumors from The Cancer Genome Atlas (TCGA).
methodWe have conducted a genome-wide analysis of differential DNA methylation and gene/miRNA expression using data from 36 CCA tumor and 9 normal samples from TCGA. The impact of DNA methylation in promoters and long-range distal enhancers on the regulation and expression of CCA-associated genes was examined using linear regression. Next, we conducted network analyses on genes which are regulated by DNA methylation as well as by miRNA. Finally, we performed Kaplan-Meier and Cox proportional hazards regression analyses in order to identify the role of selected methylation sites and specific genes and miRNAs in patient survival. We also performed real-time quantitative PCR (qPCR) to confirm the change in gene expression in CCA patients' tumor and adjacent normal samples.
resultsAltered DNA methylation was observed on 12,259 CpGs across all chromosomes, of which 78% were hypermethylated. We observed a strong negative relationship between promoter hypermethylation and corresponding gene expression in 92% of the CpGs. Differential expression analyses revealed altered expression patterns in 3,305 genes and 101 miRNAs. Finally, we identified 17 differentially methylated promoter CpGs, 72 differentially expressed genes, and two miRNAs that are likely associated with patient survival. Pathway analysis suggested that cell division, bile secretion, amino acid metabolism, PPAR signaling, hippo signaling were highly affected by gene expression and DNA methylation alterations. The qPCR analysis further confirmed that MDK, HNF1B, PACS1, and GLUD1 are differentially expressed in CCA.
conclusionBased on the survival analysis, we conclude that DEPDC1, FUT4, MDK, PACS1, PIWIL4 genes, miR-22, miR-551b microRNAs, and cg27362525 and cg26597242 CpGs can strongly support their use as prognostic markers of CCA.
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