ArticleEpigenetics2014
Epigenetic inactivation of the novel candidate tumor suppressor gene ITIH5 in colon cancer predicts unfavorable overall survival in the CpG island methylator phenotype.
Article in Epigenetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Global differences in the prevalence of the CpG island methylator phenotype of colorectal cancer.BMC cancer · 2019Pooled it
- High Expression of the Tumor Suppressor Protein ITIH5 in Cholangiocarcinomas Correlates with a Favorable Prognosis.Cancers · 2024Article
- Genetic deletion of ITIH5 leads to increased development of adipose tissue in mice.Biological research · 2024Article
- Combination of dual JAK/HDAC inhibitor with regorafenib synergistically reduces tumor growth, metastasis, and regorafenib-induced toxicity in colorectal cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- ITIH5 as a multifaceted player in pancreatic cancer suppression, impairing tyrosine kinase signaling, cell adhesion and migration.Molecular oncology · 2024Article
- An Overview on the Emerging Role of the Plasma Protease Inhibitor Protein ITIH5 as a Metastasis Suppressor.Cell biochemistry and biophysics · 2024Review
- The function of the inter-alpha-trypsin inhibitors in the development of disease.Frontiers in medicine · 2024Review
- ITIH5-Derived Polypeptides Covering the VIT Domain Suppress the Growth of Human Cancer Cells In Vitro.Cancers · 2022Article
- Long noncoding RNA LINC00261 upregulates ITIH5 to impair tumorigenic ability of pancreatic cancer stem cells.Cell death discovery · 2021Article
- ITIH5, a p53-responsive gene, inhibits the growth and metastasis of melanoma cells by downregulating the transcriptional activity of KLF4.Cell death & disease · 2021Article
- Article
- Comprehensive analysis of lncRNAs NAging · 2021Article
- ITIH5 shows tumor suppressive properties in cervical cancer cells grown as multicellular tumor spheroids.American journal of translational research · 2021Article
- The Inter-α-Trypsin Inhibitor Family: Versatile Molecules in Biology and Pathology.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2020Review
- Article
- Identification of Transcription Factor/Gene Axis in Colon Cancer Using a Methylome Approach.Frontiers in genetics · 2020Article
- A Retrospective Analysis of the Cartilage Kunitz Protease Inhibitory Proteins Identifies These as Members of the Inter-α-Trypsin Inhibitor Superfamily with Potential Roles in the Protection of the Articulatory Surface.International journal of molecular sciences · 2019Article
- Genetic variations using whole-exome sequencing might predict response for neoadjuvant chemoradiotherapy in locally advanced rectal cancer.Medical oncology (Northwood, London, England) · 2018Article
- A Strategy for Discovery of Endocrine Interactions with Application to Whole-Body Metabolism.Cell metabolism · 2018Article
- Identifying DNA methylation biomarkers for non-endoscopic detection of Barrett's esophagus.Science translational medicine · 2018Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inter-α-trypsin inhibitor heavy chain 5 (ITIH5) is supposed to be involved in extracellular matrix stability and thus may play a key role in the inhibition of tumor progression. The current study is the first to analyze in depth ITIH5 expression as well as its potential clinical and functional impact in colon cancer. Based on 30 tumor and 30 adjacent normal tissues we examined ITIH5 mRNA expression and promoter methylation, whose significance was further validated by independent data sets from The Cancer Genome Atlas (TCGA) platform. In addition, ITIH5 protein expression was evaluated using immunohistochemistry. ITIH5 mRNA expression loss was significantly associated (P<0.001) with hypermethylation of the ITIH5 promoter in primary colon tumors. In addition, treatment of tumor cell lines with demethylating (DAC) and histone acetylating (TSA) agents induced ITIH5 expression. In line, independent TCGA data revealed a significant expression loss of ITIH5, particularly in the MSI-high and CIMP-positive phenotype concordant with an increased ITIH5 hypermethylation in CIMP-positive colon tumors (P<0.001). In proximal, i.e., right-sided tumors, abundant ITIH5 expression was associated with longer overall survival (OS, P = 0.049) and the CIMP-positive (P = 0.032) subgroup. Functionally, ITIH5 re-expression mediated a reduced proliferation in HCT116 and CaCo2 cells. In conclusion, our results indicate that ITIH5 is a novel putative tumor suppressor gene in colon cancer with a potential impact in the CIMP-related pathway. ITIH5 may serve as a novel epigenetic-based diagnostic biomarker with further clinical impact for risk stratification of CIMP-positive colon cancer patients.
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