DNA methylation of GHSR, GNG4, HOXD9 and SALL3 is a common epigenetic alteration in thymic carcinoma

Kishibuchi, Reina; Kondo, Kazuya; Soejima, Shiho; Tsuboi, Mitsuhiro; Kajiura, Koichiro; Kawakami, Yukikiyo; Kawakita, Naoya; Sawada, Toru; Toba, Hiroaki; Yoshida, Misao; Takizawa, Hiromitsu; Tangoku, Akira

doi:10.3892/ijo.2019.4915

Cited by 21 publications

(30 citation statements)

References 28 publications

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“…HOXB2, B3, B4, B7 and B9 genes which we observed their upregulation in association with endometriosis, was previously shown that are in contribution with endometriosis, and also are involved in progression and development of many cancers [27,[31][32][33][34][35][36][37][38][39]. About HOXC6, C8, C9, C10, C11, C12 and C13 genes which were analyzed here, no other studies have paid attention to the relationship between these genes and endometriosis, although their involvement with female reproductive tract are vastly shown [29].…”

Section: Go Annotation Analysissupporting

confidence: 65%

Network-based bioinformatics analysis of HOX genes and their related genes in endometriosis

Chitsazian

Favaedi

Jahromi

et al. 2020

Preprint

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Background: Dysregulation of some HOX genes are important for the development of endometriosis. Endometriosis is a complex gynecologic disorder affecting as many as 10-15% of premenopausal women. The pathogenesis of endometriosis, as the presence of endometrium-like tissue outside the uterine cavity, is largely unknown. HOX genes, encoding homeodomain transcription factors, are dynamically expressed in endometrium, in which they are necessary for endometrial growth, differentiation, and implantation. Few investigations have been studied in this vast range of HOX genes with a network-based view. Network theory allows for a holistic understanding of the role of genes in diseases. The purpose of this study is to identify genes that cause this disease by focusing on the HOX family genes and their regulatory genes. Materials & Methods: Fifteen samples of eutopic and ectopic endometrium collected from patients in proliferation phase. PCR array was performed on sample groups for 84 HOX genes and their related genes. The statistical significance was determined by using t-test. PCA and Hierarchical clustering were carried out between different groups. The genes co-expression networks were constructed based on correlation between normalized gene expression data. Gene function was annotated based on Gene Ontology, the intervention in other diseases and expression in other tissues using the DAVID to clarify the function of important genes and the mechanism of endometriosis. Results: Among the analyzed genes, 30, 40 and 35 significantly differentially expressed genes were in eutopic, ectopic compared with normal and ectopic with eutopic samples, respectively. Twenty-eight genes had no significant alteration in none of the sample groups. Conclusion: The most significant genes and the genes in co-expression networks are effective genes in development, metabolic and neural processes. Another important point is that the some non-differently expressed genes in networks have many interactions with the significant genes, indicating that these non-significant genes also are likely contributed in endometriosis. Keywords: endometriosis, HOX, PCR-array, Co-expression network

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Section: Go Annotation Analysissupporting

confidence: 65%

Network-based bioinformatics analysis of HOX genes and their related genes in endometriosis

Chitsazian

Favaedi

Jahromi

et al. 2020

Preprint

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“…Some studies have shown that high expression of HOXA10-AS in lung adenocarcinoma [46] and glioma [47] can promote tumor progression. According to the risk model, hypermethylation and low expression of HOXA10-AS can increase patient survival risk, which may be related to the heterogeneity of different [48] found that promoter methylation of HOXD9 was significantly higher in thymic carcinoma than in thymoma and the thymus, and relapse-free survival was significantly worse in tumors with a higher DNA methylation of HOXD9 in all of the thymic epithelial tumors. Similar to the results of this study, hypermethylation of HOXD9 was positively correlated with high risk score.…”

Section: Discussionmentioning

confidence: 99%

Identification of methylation-driven genes related to the prognosis of papillary renal cell carcinoma: a study based on The Cancer Genome Atlas

et al. 2020

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Background: Aberrant DNA methylation patterns are involved in the pathogenesis of papillary renal cell carcinoma (pRCC). This study aimed to investigate the potential of methylation-driven genes as biomarkers in determining the prognosis of pRCC by bioinformatics analysis. Methods: DNA methylation and transcriptome profiling data were downloaded from The Cancer Genome Atlas database. Methylation-driven genes (MDGs) were obtained using MethylMix R package. A Cox regression model was used to screen for pRCC prognosis-related MDGs, and a linear risk model based on MDG methylation profiles was constructed. A combined methylation and gene expression survival analysis was performed to further explore the prognostic value of MDGs independently. Results: A total of 31 MDGs were obtained. Univariate and multivariate Cox regression analysis identified eight genes (CASP1, CD68, HOXD3, HHLA2, HOXD9, HOXA10-AS, TMEM71, and PLA2G16), which were used to construct a predictive model associated with overall survival in pRCC patients. Combined DNA methylation and gene expression survival analysis revealed that C19orf33, GGT6, GIPC2, HHLA2, HOXD3, HSD17B14, PLA2G16, and TMEM71 were significantly associated with patients' survival. Conclusion: Through the analysis of MDGs in pRCC, this study identified potential biomarkers for precision treatment and prognosis prediction, and provided the basis for future research into the molecular mechanism of pRCC.

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“…Petrini et al (14) demonstrated that GTF2IL424H mutations were the most common in type A and AB thymomas. Limited information is currently available on epigenetic alterations in TET (15)(16)(17)(18). We previously reported that the aberrant methylation of 4 cancer-related genes (DAPK, p16, MGMT, and HPP1) was significantly more frequent in TC than in thymomas (15,16).…”

Section: Gad1 Expression and Its Methylation As Indicators Of Malignant Behavior In Thymic Epithelial Tumorsmentioning

confidence: 99%

GAD1 expression and its methylation as indicators of malignant behavior in thymic epithelial tumors

et al. 2021

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Thymic epithelial tumors (TETs) comprise thymomas and thymic carcinoma (TC). TC has more aggressive features and a poorer prognosis than thymomas. Genetic and epigenetic alterations in thymomas and TC have been investigated in an attempt to identify novel target molecules for TC. In the present study, genome-wide screening was performed on aberrantly methylated CpG islands in thymomas and TC, and the glutamate decarboxylase 1 gene (GAD1) was identified as the 4th significantly hypermethylated CpG island in TC compared with thymomas. GAD1 catalyzes the production of γ-aminobutyric acid from L-glutamic acid. GAD1 expression is abundant in the brain but rare in other tissues, including the thymus. A total of 73 thymomas and 17 TC tissues were obtained from 90 patients who underwent surgery or biopsy at Tokushima University Hospital between 1990 and 2017. DNA methylation was examined by bisulfite pyrosequencing, and the mRNA and protein expression levels of GAD1 were analyzed using reverse transcription-quantitative PCR and immunohistochemistry, respectively. The DNA methylation levels of GAD1 were significantly higher in TC tissues than in the normal thymus and thymoma tissues, and GAD1 methylation exhibited high sensitivity and specificity for discriminating between TC and thymoma. The mRNA and protein expression levels of GAD1 were significantly higher in TC tissues than in thymomas. Patients with TET with high GAD1 DNA hypermethylation and high mRNA and protein expression levels had significantly shorter relapse-free survival rates than those with low levels. In conclusion, significantly more epigenetic alterations were observed in TC tissues compared with in thymomas, which may contribute to the clinical features and prognosis of patients.

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DNA methylation of GHSR, GNG4, HOXD9 and SALL3 is a common epigenetic alteration in thymic carcinoma

Cited by 21 publications

References 28 publications

Network-based bioinformatics analysis of HOX genes and their related genes in endometriosis

Network-based bioinformatics analysis of HOX genes and their related genes in endometriosis

Identification of methylation-driven genes related to the prognosis of papillary renal cell carcinoma: a study based on The Cancer Genome Atlas

GAD1 expression and its methylation as indicators of malignant behavior in thymic epithelial tumors

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