Integrative analysis of DNA methylation and gene expression profiles to identify biomarkers of glioblastoma

Alivand, Mohammad Reza; Najafi, Sajad; Esmaeili, Sajjad; Rahmanpour, Dara; Zhaleh, Hossein; Rahmati, Yazdan

doi:10.1016/j.cancergen.2021.10.008

Cited by 12 publications

(10 citation statements)

References 40 publications

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“…This may be due to low decrease in 5mC level in EGCG-treated MCF-7 cell line and greater 5mC decrease in EGCG-treated T47D cell line. However, a recent study revealed that IFI16 is hypomethylated in glioblastoma ( 56 ). To the best of our knowledge, EGCG-mediated reactivation of the IFI16 gene by decreasing promoter methylation has not previously been reported.…”

Section: Discussionmentioning

confidence: 99%

A study on DNA methylation modifying natural compounds identified EGCG for induction of IFI16 gene expression related to the innate immune response in cancer cells

2022

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Innate immune sensor IFN-induced protein 16 (IFI16) exhibits anti-inflammatory effects via IFNβ and IFN-stimulated gene (ISG)15 induction in cancer cells. Epigallocatechin gallate (EGCG) is a potent natural DNA methyltransferase inhibitor (DNMTi). Previous studies revealed that conventional DNMTis, such as 5-azacytidine (5-aza-dc), induce IFI16 expression and EGCG decreases DNMT mRNA expression and global methylation (5mC) level via promoter demethylation of tumor suppressor genes in cancer cell lines. To the best of our knowledge, however, EGCG-mediated IFI16 promoter methylation status has been overlooked. Here, initial screening was performed to determine IFI16 expression and its correlation with DNMTs in cancer cell lines from various databases. Following treatment of breast cancer cell lines with 5-aza-dc, vitamin C and EGCG, expression levels of IFI16 and its downstream transcription targets IFNβ1 and ISG15 were assessed using RT-qPCR, and the 5mC level was assessed using ELISA. In silico molecular docking simulation was performed for all DNMTs to predict the mode of ligands binding with proteins. Finally, promoter methylation level in IFI16 gene was assessed following EGCG treatment. EGCG treatment induced IFI16 expression, interacted with certain amino acids residues in DNMT proteins and decreased 5mC level and promoter methylation of IFI16. The present results may provide a basis for targeting IFI16 expression as a therapeutic option in breast cancer cell lines.

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Section: Discussionmentioning

confidence: 99%

A study on DNA methylation modifying natural compounds identified EGCG for induction of IFI16 gene expression related to the innate immune response in cancer cells

2022

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“…More and more studies have confirmed the functional interaction between PCLAF and tumors ( 8 , 10 , 11 , 52 , 53 ). Numerous studies have performed immunohistochemical analysis of various tumor tissues, which strongly suggest that PCLAF is highly expressed in a variety of tumor tissues and may serve as a pan-cancer prognostic biomar ker ( 13 , 42 , 43 , 46 – 50 , 54 , 55 ). Yet, the pathogenesis of PCLAF in different tumors is still unclear, and further research is needed.…”

Section: Discussionmentioning

confidence: 99%

Pan‑cancer analyses reveal the regulation and clinical outcome association of PCLAF in human tumors

et al. 2022

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Studies have shown that PCNA clamp associated factor (PCLAF) plays a paramount role in a variety of cancers; however, the expression profile and the specific molecular mechanism of PCLAF in cancer remains unclear, as is its value in the human pan-cancer analysis. Based on the publicly available datasets of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), a comprehensive analysis of the probable carcinogenic effects of the PCLAF gene was performed in 33 human cancers. It was found that PCLAF is highly expressed in cancer tissues compared with normal tissues, and is significantly correlated with poor prognosis. We found that the eight tumors with significantly high PCLAF expression presented with decreased DNA methylation levels of PCLAF, including cholangiocarcinoma (CHOL), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), glioblastoma multiforme (GBM), pheochromocytoma and paraganglioma (PCPG), sarcoma (SARC), testicular germ cell tumor (TGCT), stomach adenocarcinoma (STAD), and uterine corpus endometrial carcinoma (UCEC). The expression of PCLAF was found to be positively correlated with activated CD4 T cells (Act CD4) and type 2 T helper (Th2) cells, suggesting that PCLAF may play a particular role in tumor immune infiltration. In addition, the functional mechanism of PCLAF also involves the mitotic cell cycle process, cell division, and DNA replication. Our first pan-cancer study provides a relatively extensive understanding of the carcinogenic effects of PCLAF in miscellaneous tumors.

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“…R package “limma” and Wilcoxon test were used to identify LLPS-related genes (LRGs) between PCa cases and normal cases in TCGA datasets. Importantly, the cut-off value was set as FDR (false discovery rate) < 0.05 and log2 |fold change ( FC )| > 1 [ 45 ]. Then, a Venn diagram was used to filter differentially expressed RRGs (DERRGs) by taking the intersection of DEGs and RRGs.…”

Section: Methodsmentioning

confidence: 99%

A Liquid–Liquid Phase Separation-Related Index Associate with Biochemical Recurrence and Tumor Immune Environment of Prostate Cancer Patients

You

Chen

et al. 2023

IJMS

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To identify liquid–liquid phase separation (LLPS)-related molecular clusters, and to develop and validate a novel index based on LLPS for predicting the prognosis of prostate cancer (PCa) patients. We download the clinical and transcriptome data of PCa from TCGA and GEO database. The LLPS-related genes (LRGs) were extracted from PhaSepDB. Consensus clustering analysis was used to develop LLPS-related molecular subtypes for PCa. The LASSO cox regression analysis was performed to establish a novel LLPS-related index for predicting biochemical recurrence (BCR)-free survival (BCRFS). Preliminary experimental verification was performed. We initially identified a total of 102 differentially expressed LRGs for PCa. Three LLPS related molecular subtypes were identified. Moreover, we established a novel LLPS related signature for predicting BCRFS of PCa patients. Compared to low-risk patients in the training cohort, testing cohort and validating cohort, high-risk populations meant a higher risk of BCR and significantly poorer BCRFS. The area under receiver operating characteristic curve were 0.728, 0.762, and 0.741 at 1 year in the training cohort, testing cohort and validating cohort. Additionally, the subgroup analysis indicated that this index was especially suitable for PCa patients with age ≤ 65, T stage III-IV, N0 stage or in cluster 1. The FUS, which was the potential biomarker related to PCa liquid–liquid phase separation, was preliminarily identified and verified. This study successfully developed three LLPS-related molecular subtypes and identified a novel LLPS related molecular signature, which performed well in predicting BCRFS of PCa.

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Integrative analysis of DNA methylation and gene expression profiles to identify biomarkers of glioblastoma

Cited by 12 publications

References 40 publications

A study on DNA methylation modifying natural compounds identified EGCG for induction of IFI16 gene expression related to the innate immune response in cancer cells

A study on DNA methylation modifying natural compounds identified EGCG for induction of IFI16 gene expression related to the innate immune response in cancer cells

Pan‑cancer analyses reveal the regulation and clinical outcome association of PCLAF in human tumors

A Liquid–Liquid Phase Separation-Related Index Associate with Biochemical Recurrence and Tumor Immune Environment of Prostate Cancer Patients

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