In silico study of cancer stage-specific DNA methylation pattern in White breast cancer patients based on TCGA dataset

Ivan, Jeremias; Patricia, Gabriella; Agustriawan, David

doi:10.1016/j.compbiolchem.2021.107498

Cited by 6 publications

(5 citation statements)

References 43 publications

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“…However, when comparison was made between early (I, II) and advanced (III) stages of BrCa, no difference was observed in the methylation pattern of PA CGs, but only in two gene body CGs, and no changes in mRNA expression, suggesting minor ENPP2 methylation events in the course of the disease. Another study based on TCGA datasets analysis reported ENPP2 as one of 66 significantly hypermethylated genes with logFC > 1.8 between Stage I–III BrCa [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

ENPP2 Promoter Methylation Correlates with Decreased Gene Expression in Breast Cancer: Implementation as a Liquid Biopsy Biomarker

Παναγοπούλου

Drosouni

Fanidis

et al. 2022

IJMS

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Autotaxin (ATX), encoded by the ctonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) gene, is a key enzyme in lysophosphatidic acid (LPA) synthesis. We have recently described ENPP2 methylation profiles in health and multiple malignancies and demonstrated correlation to its aberrant expression. Here we focus on breast cancer (BrCa), analyzing in silico publicly available BrCa methylome datasets, to identify differentially methylated CpGs (DMCs) and correlate them with expression. Numerous DMCs were identified between BrCa and healthy breast tissues in the gene body and promoter-associated regions (PA). PA DMCs were upregulated in BrCa tissues in relation to normal, in metastatic BrCa in relation to primary, and in stage I BrCa in relation to normal, and this was correlated to decreased mRNA expression. The first exon DMC was also investigated in circulating cell free DNA (ccfDNA) isolated by BrCa patients; methylation was increased in BrCa in relation to ccfDNA from healthy individuals, confirming in silico results. It also differed between patient groups and was correlated to the presence of multiple metastatic sites. Our data indicate that promoter methylation of ENPP2 arrests its transcription in BrCa and introduce first exon methylation as a putative biomarker for diagnosis and monitoring which can be assessed in liquid biopsy.

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Section: Discussionmentioning

confidence: 99%

ENPP2 Promoter Methylation Correlates with Decreased Gene Expression in Breast Cancer: Implementation as a Liquid Biopsy Biomarker

Παναγοπούλου

Drosouni

Fanidis

et al. 2022

IJMS

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“…The methodology utilized was based on previous papers with detection of gene expressions through the steps of retrieving the data, processing the data, and creating a differential analysis from the expressions (Bernard and Agustriawan, 2019;Ivan, Patricia et al, 2021).…”

Section: Methodsmentioning

confidence: 99%

ANALISIS GEN KOMPARATIF KARSINOMA SEL SKUAMOSA PARU-PARU ANTARA INDIVIDU MEROKOK DAN TIDAK MEROKOK [Comparative Gene Analysis of Squamous Cell Lung Carcinoma Between Smoking and Non-smoking Individuals]

Shemuel,

Angelique,

Josephine

et al. 2023

Berita Biologi

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Squamous cell lung carcinoma (SCC) is a form of non-small cell lung cancer that commonly arises in the primary airway. The development of SCC is closely linked to changes in squamous cells that line the airways, primarily caused by exposure to tobacco smoke. To gain insights into SCC, bioinformatics techniques have been employed to detect biomarkers and analyze gene expression patterns, utilizing data from the Cancer Genome Atlas (TCGA) database, which was preprocessed for analysis. By employing DESeq2, a differential gene expression analysis method, identified genes showed significant variations in expression between smoking and non-smoking groups among the 11,530 genes examined. Notably, five genes, namely CT45A1, GCGR, TPTE, ABCC2, and PI16, were found to play a significant role in tumor development and were susceptible to under- or over-expression due to smoking. The majority of these genes were found to be underexpressed rather than overexpressed. These identified genes hold potential as biomarkers for tumor development and exhibit a strong correlation between smoking history and the development of SCC. However, a limitation encountered during this analysis was the unavailability of data from normal non-tumor patients, which could have facilitated a more comprehensive analysis of differential gene expression. Furthermore, this research gives a deeper implementation regarding the molecular mechanisms and genomics underlying SCC development, identifies differentially expressed genes associated with SCC and smoking history, and highlights potential biomarkers that warrant further investigation.

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“…This methylation pattern hence appeared to occur early in breast cancer development and did not significantly change with more advanced disease [ 47 ]. If fact, analysis of data from TCGA demonstrate that ENPP2 is of one of the 66 most hypermethylated genes in stage 1-3 breast cancer [ 48 ]. Whether this methylation is a protective event of the host organism to suppress tumor development is unknown, but these studies demonstrate that despite breast cancer cells displaying the propensity to overexpress ATX, they are prevented from doing so even at early stages, and instead must rely on inducing ATX in the surrounding tumor stroma to induce LPA-mediated tumorigenesis [ 49 , 50 ].…”

Section: Insights Into Atx Production In the Breast Tumor Microenviro...mentioning

confidence: 99%

Autotaxin and Lysophosphatidate Signaling: Prime Targets for Mitigating Therapy Resistance in Breast Cancer

Benesch,

Tang,

Brindley

et al. 2024

World J Oncol

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Overcoming and preventing cancer therapy resistance is the most pressing challenge in modern breast cancer management. Consequently, most modern breast cancer research is aimed at understanding and blocking these therapy resistance mechanisms. One increasingly promising therapeutic target is the autotaxin (ATX)-lysophosphatidate (LPA)-lipid phosphate phosphatase (LPP) axis. Extracellular LPA, produced from albumin-bound lysophosphatidylcholine by ATX and degraded by the ecto-activity of the LPPs, is a potent cell-signaling mediator of tumor growth, invasion, angiogenesis, immune evasion, and resistance to cancer treatment modalities. LPA signaling in the post-natal organism has central roles in physiological wound healing, but these mechanisms are subverted to fuel pathogenesis in diseases that arise from chronic inflammatory processes, including cancer. Over the last 10 years, our understanding of the role of LPA signaling in the breast tumor microenvironment has begun to mature. Tumor-promoting inflammation in breast cancer leads to increased ATX production within the tumor microenvironment. This results in increased local concentrations of LPA that are maintained in part by decreased overall cancer cell LPP expression that would otherwise more rapidly break it down. LPA signaling through six G-protein-coupled LPA receptors expressed by cancer cells can then activate virtually every known tumorigenic pathway. Consequently, to target therapy resistance and tumor growth mediated by LPA signaling, multiple inhibitors against the LPA signaling axis are entering clinical trials. In this review, we summarize recent developments in LPA breast cancer biology, and illustrate how these novel therapeutics against the LPA signaling pathway may be excellent adjuncts to extend the efficacy of evolving breast cancer treatments.

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In silico study of cancer stage-specific DNA methylation pattern in White breast cancer patients based on TCGA dataset

Cited by 6 publications

References 43 publications

ENPP2 Promoter Methylation Correlates with Decreased Gene Expression in Breast Cancer: Implementation as a Liquid Biopsy Biomarker

ENPP2 Promoter Methylation Correlates with Decreased Gene Expression in Breast Cancer: Implementation as a Liquid Biopsy Biomarker

ANALISIS GEN KOMPARATIF KARSINOMA SEL SKUAMOSA PARU-PARU ANTARA INDIVIDU MEROKOK DAN TIDAK MEROKOK [Comparative Gene Analysis of Squamous Cell Lung Carcinoma Between Smoking and Non-smoking Individuals]

Autotaxin and Lysophosphatidate Signaling: Prime Targets for Mitigating Therapy Resistance in Breast Cancer

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