Dickkopf-1 in human oral cancer

Ogoshi, Kenji; Kasamatsu, Atsushi; Iyoda, Manabu; Sakuma, Kei; Yamatoji, Masanobu; Sakamoto, Yosuke; Ogawara, Katsunori; Shiiba, Masashi; Tanzawa, Hideki; Uzawa, Katsuhiro

doi:10.3892/ijo.2011.1046

Cited by 14 publications

(8 citation statements)

References 33 publications

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“…The methylation of DKK1 may be considered a prognostic marker in oral cancer 31 . DKK1 knockdown increased cellular migration and invasiveness in oral cancer cells 32 . High expression of DKK-1 was associated with poor prognosis, and this suggests that DKK-1 may be a useful molecular marker in breast cancer 33 .…”

Section: Discussionmentioning

confidence: 92%

Comprehensive immunogenomic landscape analysis of prognosis-related genes in head and neck cancer

Wang

Lei

et al. 2020

Sci Rep

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Head and neck cancer is the sixth most common malignancy around the world, and 90% of cases are squamous cell carcinomas. In this study, we performed a systematic investigation of the immunogenomic landscape to identify prognostic biomarkers for head and neck squamous cell carcinoma (HNSCC). We analyzed the expression profiles of immune-related genes (IRGs) and clinical characteristics by interrogating RNA-seq data from 527 HNSCC patients in the cancer genome atlas (TCGA) dataset, including 41 HPV+ and 486 HPV− samples. We found that differentially expressed immune genes were closely associated with patient prognosis in HNSCC by comparing the differences in gene expression between cancer and normal samples and performing survival analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to annotate the biological functions of the differentially expressed immunogenomic prognosisrelated genes. Two additional cohorts from the Oncomine database were used for validation. 65, 56 differentially expressed IRGs was associated with clinical prognosis in total and HPVsamples, respectively. Furthermore, we extracted 10, 11 prognosis-related IRGs from 65, 56 differentially expressed IRGs, respectively. They were significantly correlated with clinical prognosis and used to construct the prognosis prediction models. The multivariable ROC curves (specifically, the AUC) were used to measure the accuracy of the prognostic models. these genes were mainly enriched in several gene ontology (GO) terms related to immunocyte migration and receptor and ligand activity. KEGG pathway analysis revealed enrichment of pathways related to cytokine−cytokine receptor interactions, which are primarily involved in biological processes. In addition, we identified 63 differentially expressed transcription factors (TFs) from 4784 differentially expressed genes, and 16 edges involving 18 nodes were formed in the regulatory network between differentially expressed TFs and the high-risk survival-associated IRGs. B cell and CD4 T cell infiltration levels were significantly negatively correlated with the expression of prognosis-related immune genes regardless of HPV status. In conclusion, this comprehensive analysis identified the prognostic IRGs as potential biomarkers, and the model generated in this study may enable an accurate prediction of survival. Head and neck cancer is a common malignancy accounting for 5-10% of cancers worldwide. Head and neck squamous cell carcinoma constitutes 90% of head and neck cancers, which arises from the pharynx, the oral cavity and lip, the ear, the larynx, the nasal cavity, the salivary glands and the paranasal sinuses 1-3. The tobacco, alcohol use and human papillomavirus (HPV) infection are important causes of head and neck squamous cell carcinoma 4. HNSCC represents a biologically complex disease process and a heterogeneous collection of tumors in which multiple pathways are altered, leading to the development of HNSCC, and the mechanisms leading to this disease...

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Section: Discussionmentioning

confidence: 92%

Comprehensive immunogenomic landscape analysis of prognosis-related genes in head and neck cancer

Wang

Lei

et al. 2020

Sci Rep

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“…As a negative control, triplicate sections were immunostained without exposure to primary antibodies. To quantify the status of the GAD1 protein expression in those components, we used an IHC scoring system to quantitatively evaluate the IHC staining, described previously [22-24]. We counted 300 cells/one field of vision.…”

Section: Methodsmentioning

confidence: 99%

Glutamate acid decarboxylase 1 promotes metastasis of human oral cancer by β-catenin translocation and MMP7 activation

et al. 2013

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BackgroundGlutamate decarboxylase 1 (GAD1), a rate-limiting enzyme in the production of γ-aminobutyric acid (GABA), is found in the GABAergic neurons of the central nervous system. Little is known about the relevance of GAD1 to oral squamous cell carcinoma (OSCC). We investigated the expression status of GAD1 and its functional mechanisms in OSCCs.MethodsWe evaluated GAD1 mRNA and protein expressions in OSCC-derived cells using real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and immunoblotting analyses. To assess the critical functions of GAD1, i.e., cellular proliferation, invasiveness, and migration, OSCC-derived cells were treated with the shRNA and specific GAD1 inhibitor, 3-mercaptopropionic acid (3-MPA). GAD1 expression in 80 patients with primary OSCCs was analyzed and compared to the clinicopathological behaviors of OSCC.ResultsqRT-PCR and immunoblotting analyses detected frequent up-regulation of GAD1 in OSCC-derived cells compared to human normal oral keratinocytes. Suppression of nuclear localization of β-catenin and MMP7 secretion was observed in GAD1 knockdown and 3-MPA-treated cells. We also found low cellular invasiveness and migratory abilities in GAD1 knockdown and 3-MPA-treated cells. In the clinical samples, GAD1 expression in the primary OSCCs was significantly (P < 0.05) higher than in normal counterparts and was correlated significantly (P < 0.05) with regional lymph node metastasis.ConclusionsOur data showed that up-regulation of GAD1 was a characteristic event in OSCCs and that GAD1 was correlated with cellular invasiveness and migration by regulating β-catenin translocation and MMP7 activation. GAD1 might play an important role in controlling tumoral invasiveness and metastasis in oral cancer.

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“…As a negative control, triplicate sections were immunostained without exposure to primary antibodies, which confirmed the staining specificity. To quantify the status of the CDCA3 protein expression in those components, we used an IHC scoring system described previously [22-26]. This IHC scoring system was established for quantitative evaluation of IHC staining.…”

Section: Methodsmentioning

confidence: 99%

Overexpression of cell cycle regulator CDCA3 promotes oral cancer progression by enhancing cell proliferation with prevention of G1 phase arrest

et al. 2012

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BackgroundCell division cycle associated 3 (CDCA3), part of the Skp1-cullin-F-box (SCF) ubiquitin ligase, refers to a trigger of mitotic entry and mediates destruction of the mitosis inhibitory kinase. Little is known about the relevance of CDCA3 to human malignancy including oral squamous cell carcinoma (OSCC). We aimed to characterize the expression state and function of CDCA3 in OSCC.MethodsWe evaluated CDCA3 mRNA and protein expression in both OSCC-derived cell lines and primary OSCCs and performed functional analyses of CDCA3 in OSCC-derived cells using the shRNA system.ResultsThe CDCA3 expression at both the mRNA and protein levels was frequently up-regulated in all cell lines examined and primary tumors (mRNA, 51/69, 74 %; protein, 79/95, 83 %) compared to normal controls (p < 0.001). In contrast, no significant level of CDCA3 protein expression was seen in oral premalignant lesions (OPLs) (n = 20) compared with the expression in OSCCs. Among the clinical variables analyzed, the CDCA3 expression status was closely related to tumor size (p < 0.05). In addition, suppression of CDCA3 expression with shRNA significantly (p < 0.05) inhibited cellular proliferation compared with the control cells by arresting cell-cycle progression at the G1 phase. Further, there was up-regulation of the cyclin-dependent kinase inhibitors (p21Cip1, p27Kip1, p15INK4B, and p16INK4A) in the knockdown cells.ConclusionThe current results showed that overexpression of CDCA3 occurs frequently during oral carcinogenesis and this overexpression might be associated closely with progression of OSCCs by preventing the arrest of cell-cycle progression at the G1 phase via decreased expression of the cyclin-dependent kinase inhibitors.

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Dickkopf-1 in human oral cancer

Cited by 14 publications

References 33 publications

Comprehensive immunogenomic landscape analysis of prognosis-related genes in head and neck cancer

Comprehensive immunogenomic landscape analysis of prognosis-related genes in head and neck cancer

Glutamate acid decarboxylase 1 promotes metastasis of human oral cancer by β-catenin translocation and MMP7 activation

Overexpression of cell cycle regulator CDCA3 promotes oral cancer progression by enhancing cell proliferation with prevention of G1 phase arrest

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