Hypermethylation of ITGA4, TFPI2 and VIMENTIN promoters is increased in inflamed colon tissue: putative risk markers for colitis-associated cancer

Gerecke, Christian; Scholtka, Bettina; Löwenstein, Yvonne; Fait, Isabel; Gottschalk, Uwe; Rogoll, Dorothee; Melcher, Ralph; Kleuser, Burkhard

doi:10.1007/s00432-015-1972-8

Cited by 49 publications

(45 citation statements)

References 44 publications

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“…CNN3 is involved in the regulation of cell migration and the placentation process . TFPI2 encodes a Kunitz‐type serine proteinase inhibitor with inhibitory function against tumor growth and metastasis; protecting the extracellular matrix of cancer cells from degradation and tumor invasion . COL17A1 encodes collagen XVII (COL17), a transmembrane protein that is an essential component of type I hemidesmosomes and acts as a cell‐matrix adhesion molecule .…”

Section: Discussionmentioning

confidence: 99%

Establishment of a novel experimental model for muscle‐invasive bladder cancer using a dog bladder cancer organoid culture

et al. 2019

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In human and dogs, bladder cancer (BC) is the most common neoplasm affecting the urinary tract. Dog BC resembles human muscle‐invasive BC in histopathological characteristics and gene expression profiles, and could be an important research model for this disease. Cancer patient‐derived organoid culture can recapitulate organ structures and maintains the gene expression profiles of original tumor tissues. In a previous study, we generated dog prostate cancer organoids using urine samples, however dog BC organoids had never been produced. Therefore we aimed to generate dog BC organoids using urine samples and check their histopathological characteristics, drug sensitivity, and gene expression profiles. Organoids from individual BC dogs were successfully generated, expressed urothelial cell markers (CK7, CK20, and UPK3A) and exhibited tumorigenesis in vivo. In a cell viability assay, the response to combined treatment with a range of anticancer drugs (cisplatin, vinblastine, gemcitabine or piroxicam) was markedly different in each BC organoid. In RNA‐sequencing analysis, expression levels of basal cell markers (CK5 and DSG3) and several novel genes (MMP28, CTSE, CNN3, TFPI2, COL17A1, and AGPAT4) were upregulated in BC organoids compared with normal bladder tissues or two‐dimensional (2D) BC cell lines. These established dog BC organoids might be a useful tool, not only to determine suitable chemotherapy for BC diseased dogs but also to identify novel biomarkers in human muscle‐invasive BC. In the present study, for the 1st time, dog BC organoids were generated and several specifically upregulated organoid genes were identified. Our data suggest that dog BC organoids might become a new tool to provide fresh insights into both dog BC therapy and diagnostic biomarkers.

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Section: Discussionmentioning

confidence: 99%

Establishment of a novel experimental model for muscle‐invasive bladder cancer using a dog bladder cancer organoid culture

et al. 2019

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“…20 TFPI2 can play as a critical roles involved in protecting the extracellular matrix of cancer cells from degradation as well as regulating tumor invasion. 21 Abnormal promoter hypermethylation of TFPI2 has been observed in CRC, 22 gastric cancer, 23 hepatocellular carcinoma, 24 pancreatic cancer, 25 and cervical cancer. 26 Moreover, promoter hypermethylation of TFPI2 has been detected in recurrence and early-stage CRC, 27 and in sera from CRC patients with large, poorly differentiated carcinomas, invasion, and several metastasis such as lymph node or distant.…”

Section: Discussionmentioning

confidence: 99%

Hypermethylated promoters of tumor suppressor genes were identified in Crohn’s disease patients

Kim

Han

2020

Intest Res

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Background/Aims: Overwhelming evidence suggests that inflammatory bowel disease (IBD) is caused by a complicated interplay between the multiple genes and abnormal epigenetic regulation in response to environmental factors. It is becoming apparent that epigenetic factors are significantly associated with the development of the disease. DNA methylation remains the most studied epigenetic modification, and hypermethylation of gene promoters is associated with gene silencing.Methods: DNA methylation alterations may contribute to the many complex diseases development by regulating the interplay between external and internal environmental factors and gene transcriptional expression. In this study, we used 15 tumor suppressor genes (TSGs), originally identified in colon cancer, to detect promoter methylation in patients with Crohn’s disease (CD). Methylation specific polymerase chain reaction and bisulfite sequencing analyses were performed to assess methylation level of TSGs in CD patients.Results: We found 6 TSGs (sFRP1, sFRP2, sFRP5, TFPI2, Sox17, and GATA4) are robustly hypermethylated in CD patient samples. Bisulfite sequencing analysis confirmed the methylation levels of the sFRP1, sFRP2, sFRP5, TFPI2, Sox17, and GATA4 promoters in the representative CD patient samples.Conclusions: In this study, the promoter hypermethylation of the TSGs observed indicates that CD exhibits specific DNA methylation signatures with potential clinical applications for the noninvasive diagnosis of IBD and the prognosis for patients with IBD.

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“…Our literature review resulted in the selection of seven target genes. These genes were previously reported to exhibit DNA methylation ( CR2 [24], ITGA4 [25], RERG [26], RRAD [4], SHISA3 [27], ZNF549, and ZNF671 [28]). Schwab and Illges found that premature B lymphocytes contained a methylated CpG island and did not express CR2 ( CD21 ) [24].…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, viral capsid protein mediated EBV binding on CR2 [29]. Gerecke et al showed that methylation markers in the promoters of ITGA4 , TFPI2 , and VIMENTIN seemed to be suitable risk markers for inflammation-associated colon cancer [25], and Chang et al demonstrated ITGA4 , SFRP2 , and p16 promoter methylation in stool samples from patients with colorectal adenomas and carcinoma [30]. RERG was reported to be a tumor suppressor gene in colorectal cancer [31] and breast cancer [26].…”

Section: Discussionmentioning

confidence: 99%

Quantitation of DNA methylation in Epstein-Barr virus–associated nasopharyngeal carcinoma by bisulfite amplicon sequencing

Zhao

Wang

et al. 2017

BMC Cancer

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BackgroundEpigenetic changes, including DNA methylation, disrupt normal cell function, thus contributing to multiple steps of carcinogenesis. Nasopharyngeal carcinoma (NPC) is endemic in southern China and is highly associated with Epstein-Barr virus (EBV) infection. Significant changes of the host cell methylome are observed in EBV-associated NPC with cancer development. Epigenetic marks for NPC diagnosis are urgently needed. In order to explore DNA methylation marks, we investigated DNA methylation of candidate genes in EBV-associated nasopharyngeal carcinoma.MethodsWe first employed methyl-capture sequencing and cDNA microarrays to compare the genome-wide methylation profiles of seven NPC tissues and five non-cancer nasopharyngeal epithelium (NNE) tissues. We found 150 hypermethylated CpG islands spanning promoter regions and down-regulated genes. Furthermore, we quantified the methylation rates of seven candidate genes using bisulfite amplicon sequencing for nine NPC and nine NNE tissues.ResultsAll seven candidate genes showed significantly higher methylation rates in NPC than in NNE tissues, and the ratios (NPC/NNE) were in descending order as follows: ITGA4 > RERG > ZNF671 > SHISA3 > ZNF549 > CR2 > RRAD. In particular, methylation levels of ITGA4, RERG, and ZNF671 could distinguish NPC patients from NNE subjects.ConclusionsWe identified the DNA methylation rates of previously unidentified NPC candidate genes. The combination of genome-wide and targeted methylation profiling by next-generation sequencers should provide useful information regarding cancer-specific aberrant methylation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3482-3) contains supplementary material, which is available to authorized users.

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Hypermethylation of ITGA4, TFPI2 and VIMENTIN promoters is increased in inflamed colon tissue: putative risk markers for colitis-associated cancer

Abstract: The already established methylation marker VIM does not permit a specific and sensitive discrimination of healthy and neoplastic tissue. The methylation markers ITGA4 and TFPI2 seem to be suitable risk markers for inflammation-associated colon cancer.

Cited by 49 publications

References 44 publications

Establishment of a novel experimental model for muscle‐invasive bladder cancer using a dog bladder cancer organoid culture

Establishment of a novel experimental model for muscle‐invasive bladder cancer using a dog bladder cancer organoid culture

Hypermethylated promoters of tumor suppressor genes were identified in Crohn’s disease patients

Quantitation of DNA methylation in Epstein-Barr virus–associated nasopharyngeal carcinoma by bisulfite amplicon sequencing

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