ArticleJournal of translational medicine2014
Promoter hypermethylation and silencing of tissue factor pathway inhibitor-2 in oral squamous cell carcinoma.
Article in Journal of translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- TFPI2 expression predicts resistance to immunotherapy plus tyrosine kinase inhibitor and informs first-line therapy selection in metastatic renal cell carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Epigenetic downregulation of the proapoptotic geneMolecular medicine reports · 2025Article
- Tissue factor pathway inhibitor-2 (TFPI-2)-an underappreciated partaker in cancer and metastasis.Cancer metastasis reviews · 2024Review
- Identification of SLC22A17 DNA methylation hotspot as a potential biomarker in cutaneous melanoma.Journal of translational medicine · 2024Article
- Restoration of TFPI2 by LSD1 inhibition suppresses tumor progression and potentiates antitumor immunity in breast cancer.Cancer letters · 2024Article
- Curcumin inhibits the invasion and migration of pancreatic cancer cells by upregulating TFPI-2 to regulate ERK- and JNK-mediated epithelial-mesenchymal transition.European journal of nutrition · 2024Article
- rTFPI Protects Cardiomyocytes from Hypoxia/Reoxygenation Injury through Inhibiting Autophagy and the Class III PI3K/Beclin-1 Pathway.Cell biochemistry and biophysics · 2023Article
- Validation of tissue factor pathway inhibitor 2 as a specific biomarker for preoperative prediction of clear cell carcinoma of the ovary.International journal of clinical oncology · 2021Article
- Identification and Confirmation of the miR-30 Family as a Potential Central Player in Tobacco-Related Head and Neck Squamous Cell Carcinoma.Frontiers in oncology · 2021Article
- Down-regulation of tissue factor inhibits invasion and metastasis of non-small cell lung cancer.Journal of Cancer · 2020Article
- Involvement of MAFB and MAFF in Retinoid-Mediated Suppression of Hepatocellular Carcinoma Invasion.International journal of molecular sciences · 2018Article
- The role ofOncotarget · 2017Article
- TLR4 as a negative regulator of keratinocyte proliferation.PloS one · 2017Article
- Enhancing chemosensitivity in oral squamous cell carcinoma by lentivirus vector-mediated RNA interference targetingOncology letters · 2016Article
- Clinical Significance of Tissue Factor Pathway Inhibitor 2, a Serum Biomarker Candidate for Ovarian Clear Cell Carcinoma.PloS one · 2016Article
- Correlation and prognostic significance of MMP-2 and TFPI-2 differential expression in pancreatic carcinoma.International journal of clinical and experimental pathology · 2015Article
- DNA methylation profiles and biomarkers of oral squamous cell carcinoma.Epigenetics · 2015Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe treatment of oral squamous cell carcinoma (OSCC) following early detection is associated with good outcomes. Therefore, the survival and prognosis of OSCC patients could be hugely improved by identifying reliable biomarkers for the early diagnosis of the disease. Our previous methylation microarray analysis results have suggested that the gene encoding tissue factor pathway inhibitor-2 (TFPI-2) is a potential clinical predictor as well as a key regulator involved in OSCC malignancy.
methodsMethylation of the TFPI-2 promoter in oral tissue specimens was evaluated by bisulfite sequencing assay, quantitative methylation-specific PCR, and pyrosequencing assay. The differences in methylation levels among the groups were compared using the Mann-Whitney U test. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the discrimination ability for detecting OSCC. Cellular TFPI-2 expression was analyzed by quantitative reverse-transcription PCR before and after treatment with 5'-aza-2'-deoxycytidine and trichostatin A, to confirm whether TFPI-2 was epigenetically silenced in OSCC cells. We investigated whether TFPI-2 plays a role as a tumor suppressor by establishing TFPI-2-overexpressing OSCC cells and subjecting them to in vitro cellular proliferation, migration, and invasion assays, as well as an in vivo metastasis assay.
resultsTFPI-2 was hypermethylated in OSCC tissues versus normal oral tissues (P < 0.0001), with AUROC = 0.91, when using a pyrosequencing assay to quantify the methylation level. TFPI-2 silencing in OSCC was regulated by both DNA methylation and chromatin histone modification. Restoration of TFPI-2 counteracted the invasiveness of OSCC by inhibiting the enzymatic activity of matrix metalloproteinase-2, and consequently interfered with OSCC metastasis in vivo.
conclusionsOur data suggest strongly that TFPI-2 is a down-regulated tumor suppressor gene in OSCC, probably involving epigenetic silencing mechanisms. The loss of TFPI-2 expression is a key event for oral tumorigenesis, especially in the process of tumor metastasis.
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