Promoter hypermethylation and silencing of tissue factor pathway inhibitor-2 in oral squamous cell carcinoma

Lai, Yi-Hui; He, Ru-Yin; Chou, Jian–Liang; Chan, Michael W.Y.; Li, Yufen; Tai, Chien‐Kuo

doi:10.1186/s12967-014-0237-7

Cited by 21 publications

(17 citation statements)

References 43 publications

(52 reference statements)

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“…This finding suggests that the up-regulation of TFPI2 gene in tumor tissue is responsible for the serum level of TFPI2. By contrast, in other cancers, expression of TFPI2 is reduced or absent following aberrant methylation of its promoter region [23–27]. In addition, we recently obtained preliminary data suggesting that serum TFPI2 levels are not elevated in patients with clear cell–type renal cell carcinoma (data not shown).…”

Section: Discussionmentioning

confidence: 84%

Clinical Significance of Tissue Factor Pathway Inhibitor 2, a Serum Biomarker Candidate for Ovarian Clear Cell Carcinoma

et al. 2016

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BackgroundThere is currently no reliable serum biomarker for ovarian clear cell carcinoma (CCC), a highly lethal histological subtype of epithelial ovarian cancer (EOC). Previously, using a proteome-based approach, we identified tissue factor pathway inhibitor 2 (TFPI2) as a candidate serum biomarker for CCC. In this study, we sought to evaluate the clinical diagnostic performance of TFPI2 in preoperative prediction of CCC.MethodsSerum TFPI2 levels were measured in serum samples from a retrospective training set consisting of patients with benign and borderline ovarian tumors, EOC subtypes, and uterine diseases. Via receiver operating characteristic (ROC) analyses, we compared the diagnostic performance of TFPI2 with that of CA125 in discrimination of patients with ovarian CCC from other patient groups. The observed diagnostic performances were examined in a prospective validation set.ResultsThe 268-patient training set included 29 patients with ovarian CCC. Unlike CA125, which was also elevated in patients with endometriosis and several EOC subtypes, serum TFPI2 levels were specifically elevated only in ovarian CCC patients, consistent with the mRNA expression pattern in tumor tissues. The area under the ROC curve (AUC) of serum TFPI2 was obviously higher than that of CA125 for discrimination of CCC from other ovarian diseases (AUC = 0.891 versus 0.595). Applying a cut-off value of 280 pg/mL, TFPI2 could distinguish early-stage (FIGO I and II) CCC from endometriosis with 72.2% sensitivity, 93.3% specificity, and 88.8% accuracy. Similar results were confirmed in an independent 156-patient prospective validation set.ConclusionsTFPI2 is a useful serum biomarker for preoperative clinical diagnosis of CCC.

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Section: Discussionmentioning

confidence: 84%

Clinical Significance of Tissue Factor Pathway Inhibitor 2, a Serum Biomarker Candidate for Ovarian Clear Cell Carcinoma

et al. 2016

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“…As a transmembrane receptor of glycoprotein, TF serves as an important factor in cells to initiate the extrinsic pathway of the blood coagulation cascade and exerts its primary function through a natural high affinity interaction with its gland, factor VII (fVII), and its activated form, fVIIa [13]. Recent studies about TF were conducted in pancreatic, breast, head and neck squamous cell carcinoma, and colorectal tumor cell lines [8,[14][15][16][17]. Scholars who study the relationship between cancer and coagulation have been focused on the investigation in TF.…”

Section: Discussionmentioning

confidence: 99%

Down-regulation of tissue factor inhibits invasion and metastasis of non-small cell lung cancer

Xia¹,

Zhang²,

Chen³

et al. 2020

J. Cancer

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Objective: Tissue factor (TF) is clinically identified as a marker for the detection of various types of cancer as well as the prediction of prognosis for cancer patients. This present study aims to explore the possibility and feasibility to use plasma TF as a biomarker for the prediction of prognosis of patients with non-small cell lung cancer (NSCLC). Methods: A total of 100 patients with NSCLC at stage I to IV was included in the study, in whom the expression of plasma TF was detected. The Cox proportional-hazards regression model was then used to analyze the collected information, attempting to identify how patients' overall survival (OS) was associated with the expression of plasma TF. To verify the function of TF in invasion and metastasis, the expression of plasma TF was downregulated by SiRNA both in vivo and in vitro. Results: The expression of plasma TF in NSCLC patients was related to the diagnosis age of the patient. It was noted that patients with high TF expression levels tended to have worse OS performance, which implied that TF could be used as a marker for patients with stage I-IV NSCLC (HR = 2.030, 95% CI = 1.21-3.398, P = 0.007). TF down-regulation inhibited the growth of tumor in vitro as well as the metastasis and invasion of NSCLC cells in vivo. Conclusion: Both in vivo and in vitro, the invasion and migration of NSCLC cells are suppressed by TF knockdown. TF has the potential to become an effective biomarker for the prediction of prognosis of patients with stage I-IV NSCLC.

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“…Together with IL-6, among the downregulated genes was TFPI. TFPI is known to be involved in the formation of matrix-rich vascular-like networks in melanoma [ 51 , 52 ]; [ 53 ] and is used as a diagnostic marker for SCC [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

TLR4 as a negative regulator of keratinocyte proliferation

et al. 2017

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TLR4 is an innate immune receptor with expression in human skin, keratinocytes as well as squamous cell carcinoma (SCC) of the skin. In the present study we investigate the role of TLR4 as a negative regulator of keratinocyte proliferation. We present here that the expression of TLR4 increased with the differentiation of cultured keratinocytes in a passage-dependent manner or under calcium-rich conditions. Moreover, the down-regulation of TLR4 by specific knockdown increased the proliferation of HaCaT keratinocytes in vitro. In addition, subcutaneously injected HaCaT keratinocytes with shTLR4 formed growing tumors in nude mice. In contrast, we observed lower proliferation and increased migration in vitro of the SCC13 cell line stably overexpressing TLR4 in comparison to SCC13 TLR4 negative cells. In vivo, SCC13 TLR4-overexpressing tumors showed delayed growth in comparison to TLR4 negative tumors. The overexpression of TLR4 in SCC13 tumor cells was followed by phosphorylation of ERK1/2 and JNK and increased expression of ATF3. In gene expression arrays, the overexpression of TLR4 in tumor cells correlated with gene expression of ATF-3, IL-6, CDH13, CXCL-1 and TFPI. In summary, TLR4 negatively regulates the proliferation of keratinocytes and its overexpression reduces tumor growth of SCC cells.

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Promoter hypermethylation and silencing of tissue factor pathway inhibitor-2 in oral squamous cell carcinoma

Cited by 21 publications

References 43 publications

Clinical Significance of Tissue Factor Pathway Inhibitor 2, a Serum Biomarker Candidate for Ovarian Clear Cell Carcinoma

Clinical Significance of Tissue Factor Pathway Inhibitor 2, a Serum Biomarker Candidate for Ovarian Clear Cell Carcinoma

Down-regulation of tissue factor inhibits invasion and metastasis of non-small cell lung cancer

TLR4 as a negative regulator of keratinocyte proliferation

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