Thrombomodulin expression regulates tumorigenesis in bladder cancer

Wu, Chun–Te; Chang, Ying-Hsu; Lin, Paul; Chen, Wen‐Cheng; Chen, Miao‐Fen

doi:10.1186/1471-2407-14-375

Cited by 26 publications

(22 citation statements)

References 42 publications

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“…The THBD mRNA expression level found to be significantly and inversely correlated with tumor grade and lymph node status in both non-IBC and IBC patients. This is in agreement with a previous study of bladder cancer, which demonstrated that decreased TM expression level is a predictor of aggressiveness in advanced bladder cancer [54]. TM expression was also shown to be decreased in human prostate cancer cell lines, DU-145, LNCaP and PC-3 as compared to normal prostate epithelial cells PrEC [55].…”

Section: Discussionsupporting

confidence: 93%

IL-10 correlates with the expression of carboxypeptidase B2 and lymphovascular invasion in inflammatory breast cancer: The potential role of tumor infiltrated macrophages

Mohamed

El-Husseiny

El-Ghonaimy

et al. 2018

Current Problems in Cancer

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Pro-carboxypeptidase B2 (pro-CPB2) or thrombin-activatable ﬁbrinolysis inhibitor (TAFI) is a glycoprotein encoded by the CPB2 gene and deregulated in several cancer types, including breast cancer. Thrombin binding to thrombomodulin (TM), encoded by THBD, is important for TAFI activation. CPB2 gene expression is influenced by genetic polymorphism and cytokines such as interleukin 10 (IL-10). Our previous results showed that tumor infiltrating monocytes/macrophages (CD14/CD16) isolated from inflammatory breast cancer (IBC) patients' secrete high levels of IL-10. The aim of the present study is to test genetic polymorphism and expression of CPB2 in healthy breast tissues and carcinoma tissues of non-IBC and IBC patients. Furthermore, to investigate whether IL-10 modulates the expression of CPB2 and THBD in vivo and in-vitro. We tested CPB2 Thr325Ile polymorphism using restriction fragment length polymorphism, (RFLP) technique in healthy and carcinoma breast tissues. The mRNA expression of CPB2, THBD and IL10 were assessed by RT-qPCR. Infiltration of CD14 cells was assessed by immunohistochemistry. In addition, we investigated the correlation between infiltration of CD14 cells and expression of IL10 and CPB2. Furthermore, we correlated IL10 expression with the expression of both CPB2 and THBD in breast carcinoma tissues. Finally, we validated the role of recombinant IL-10 in regulating the expression of CPB2 and THBD using different breast cancer cell lines. Our results showed that CPB2 genotypes carrying the high-risk allele [Thr/Ile (CT) and Ile/Ile (TT)] were more frequent in both IBC and non-IBC patients compared to control group. CPB2 genotypes did not show any statistical correlation with CPB2 mRNA expression levels or patients' clinical pathological properties. Interestingly, CPB2 and IL10 expression were significantly higher and positively correlated with the incidence of CD14 cells in carcinoma tissues of IBC as compared to non-IBC. On the other hand, THBD expression was significantly lower in IBC carcinoma versus non-IBC tissues. Based on molecular subtypes, CPB2 and IL10 expression were significantly higher in triple negative (TN) as compared to hormonal positive (HP) carcinoma tissues of IBC. Moreover, CPB2 expression was positively correlated with presence of lymphovascular invasion and the expression of IL10 in carcinoma tissues of IBC patients. Furthermore, recombinant human IL-10 stimulated CPB2 expression in SUM-149 (IBC cell line) but not in MDA-MB-231 (non-IBC cell line), while there was no significant effect THBD expression. In conclusion, carcinoma tissues of IBC patients are characterized by higher expression of CPB2 and lower expression of THBD. Moreover, CPB2 positively correlates with IL10 mRNA expression, incidence of CD14 cells and lymphovascular invasion in IBC patients. IL-10 stimulated CPB2 expression in TN-IBC cell line suggests a relevant role of CPB2 in the aggressive phenotype of IBC.

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Section: Discussionsupporting

confidence: 93%

IL-10 correlates with the expression of carboxypeptidase B2 and lymphovascular invasion in inflammatory breast cancer: The potential role of tumor infiltrated macrophages

Mohamed

El-Husseiny

El-Ghonaimy

et al. 2018

Current Problems in Cancer

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“…The presence of specific biomarkers and the lack of clinical evidence to suggest another primary origin such as anus, rectum, cervix, or uterus, support our conclusion that our patient had a very rare form of primary non-urothelial squamous cell carcinoma of the bladder [9, 10]. Her case provides a noteworthy example of a rare incidental finding during an emergent clinical presentation.…”

Section: Discussionsupporting

confidence: 73%

Primary non-urothelial squamous cell carcinoma masquerading as a perforated gastric ulcer: a case report

Kaczynski¹,

Fegely²,

Nier

et al. 2019

Journal of Surgical Case Reports

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We present an 84-year-old female patient with a very rare form of primary non-urothelial squamous cell carcinoma of the bladder, found incidentally during emergency exploratory laparotomy for a perforated pre-pyloric gastric ulcer. The bladder tumor was positive for CK5/6, CK903, and thrombomodulin biomarkers, as well as for high-risk HPV (16, 18, and 31). Based on a literature review of non-urothelial bladder cancers, specifically non-bilharzial squamous cell carcinoma, we believe our patient had a very rare form of primary non-urothelial squamous cell carcinoma of the bladder. The presence of these tumor markers and the lack of clinical evidence to suggest another primary origin, such as anus, rectum, cervix, or uterus, support this conclusion. This case provides an interesting example of a very rare incidental finding during an emergent procedure.

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“…(thrombomodulin) was a membrane receptor that bound thrombin resulting in activation of protein C, degradation clotting factors Va and VIIIa and reduction of thrombin [29]. Studies had found that THBD was expressed in bladder cancer, lung cancer and other tumors, and its expression level was related to tumorigenesis, invasiveness and metastasis [30][31][32], speci cally, the expression of THBD was inversely correlated with tumor progression. There were no reports of the expression level of THBD in brain tumors, our study showed that THBD was highly expressed in GBM patients, and patients with different expression levels had inequable prognosis.…”

Section: Discussionmentioning

confidence: 99%

Identification of novel genes associated with diagnosis and prognosis in glioblastoma

Cai

Tang

et al. 2020

Preprint

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Background: Glioblastoma (GBM) is the most lethal primary brain cancer and its survival rate is very low. Comprehensive genomic characteristics and high degree of heterogeneity of GBM are main causes that contribute to the absence of effective therapeutic targets and prognostic markers and eventual treatment failures. Here, Gene set enrichment analysis (GSEA) was used to explore comprehensive genomic characteristics and high degree of heterogeneity of GBM. Our study will help explain potential tumorigenesis mechanism and contribute to development of targeted therapeutics and prediction of patient prognosis.Methods: Gene expression profile of GSE50161 was downloaded from Gene Expression Omnibus (GEO) database and GSEA was performed to evaluate the microarray data at level of gene sets of GO, KEGG and hallmark of Molecular Signatures Database (MSigDB). Core enrichments of selected hallmark gene sets were applied for clinical prognosis verification in Gene Expression Profiling Interactive Analysis (GEPIA). Genes associated with significant overall survival (OS) and unreported before were recognized as novel; the expression levels of novel genes in GBM samples and every novel gene between normal brain and GBM samples were compared. Receiver operating characteristic (ROC) and Pearson correlation analysis were also performed to evaluate the diagnostic biomarkers of GBM and correlations among novel genes respectively.Results: We obtained 511 and 494 GO gene sets, 12 and 10 KEGG gene sets, and 2 and 8 hallmark gene sets in normal and GBM samples respectively. Five novel genes SERPINA5, TENM2, ARAP3, THBD, TCF19 associated with GBM prognosis were selected and four novel genes SERPINA5, TENM2, ARAP3, TCF19 performed well for GBM diagnosis prediction were obtained. In addition, we also found that four novel genes SERPINA5, ARAP3, THBD, TCF19 that high expressed in GBM samples were all positively correlated with each other and correlation between ARAP3 and TCF19 was the strongest.Conclusions: Our study will help deeper understand the molecular heterogeneity and develop of targeted therapeutics of GBM; five novel related to prognosis genes (of which four are also related to diagnosis) may be applied to more accurate clinical decision-making process.

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Thrombomodulin expression regulates tumorigenesis in bladder cancer

Cited by 26 publications

References 42 publications

IL-10 correlates with the expression of carboxypeptidase B2 and lymphovascular invasion in inflammatory breast cancer: The potential role of tumor infiltrated macrophages

IL-10 correlates with the expression of carboxypeptidase B2 and lymphovascular invasion in inflammatory breast cancer: The potential role of tumor infiltrated macrophages

Primary non-urothelial squamous cell carcinoma masquerading as a perforated gastric ulcer: a case report

Identification of novel genes associated with diagnosis and prognosis in glioblastoma

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