Screening of Differential Promoter Hypermethylated Genes in Primary Oral Squamous Cell Carcinoma

Heah, Khor Goot; Froemming, Gabriele Ruth Anisah; Zain, Rosnah Binti; Abraham, Mannil Thomas; Thong, Kwai Lin

doi:10.7314/apjcp.2014.15.20.8957

Cited by 11 publications

(6 citation statements)

References 28 publications

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“…Regarding tumors, little is known about CELSR3. CELSR3 was previously found to correlated with small intestinal neuroendocrine tumors [24] and oral squamous cell carcinoma [25]. Regarding liver cancer, scholars have reported that CELSR3 was up-regulated in tumor stellate cells [26].…”

Section: Ivyspringmentioning

confidence: 93%

Effect of CELSR3 on the Cell Cycle and Apoptosis of Hepatocellular Carcinoma Cells

Xie

Dang

et al. 2020

J. Cancer

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Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3) has been reported in cancers but its role and potential molecular mechanism in hepatocellular carcinoma (HCC) is unclear. Therefore, we aimed to investigate the clinical value and molecular mechanism of CELSR3 in HCC using an in vitro experiment, a meta-analysis and bioinformatics. The in vitro experiment determined the promoting effect of CELSR3 in the proliferation, invasion, and migration of HCC cells. CELSR3 knockout causes S-phage arrest in HCC cells. CELSR3 can also inhibit the apoptosis of HCC cells. The expression of the CELSR3 gene and protein was significantly elevated in HCC. Elevated CELSR3 was correlated to the bigger tumor size, higher pathological stage, and the worse overall survival of HCC. Methylation analysis revealed that the hypomethylation of CELSR3 regulated by DNMT1, DNMT3A, and DNMT3B may be the underlying mechanism of upregulated CELSR3. Biological enrichment analysis uncovered that the cell cycle, DNA replication, and PI3K-Akt signaling pathways were important pathways regulated by CELSR3 and its co-expressed genes in HCC. Taken together, upregulated CELSR3 is an important regulator in the progression and prognosis of HCC. The hypomethylation of CELSR3 and its regulation in the cell cycle may be the potential molecular mechanism in HCC.

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Section: Ivyspringmentioning

confidence: 93%

Effect of CELSR3 on the Cell Cycle and Apoptosis of Hepatocellular Carcinoma Cells

Xie

Dang

et al. 2020

J. Cancer

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“…Evaluation of the combination of six genes with aberrant methylation (RARB , KLLN , CHFR , TP7 3, GSTP1 , and CASP8 ) was particularly useful for identifying early-stage oral cancer in clinically diagnosed patients with OPMDs with high diagnostic performance. RARB , KLLN , CHFR , TP73 , and CASP8 have been reported in previous studies to be associated with methylation and OSCC in tissue samples and cell lines [ 32 , 33 , 34 , 35 ]. Although GSTP1 has been reported to be associated with genetic polymorphisms and OSCC [ 36 ], we could not find any reports of an association between GSTP1 and methylation and OSCC; therefore, our results are novel.…”

Section: Discussionmentioning

confidence: 99%

Detecting Early-Stage Oral Cancer from Clinically Diagnosed Oral Potentially Malignant Disorders by DNA Methylation Profile

Mori

Hamada²,

Beppu

et al. 2022

Cancers

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Clinically, early-stage oral cancers are difficult to distinguish from oral potentially malignant disorders (OPMDs), and invasive tissue biopsy should be performed to determine a treatment strategy. Previously, we focused on gargle fluid as a noninvasive testing method and reported aberrant methylation in gargle fluid in patients with oral cancer. This study aimed to distinguish early-stage oral cancer from clinically diagnosed OPMDs using gargle fluid samples. We collected gargle fluid samples from 40 patients who were clinically diagnosed with OPMDs in the training set; among them, 9 patients were pathologically diagnosed with oral cancer. Methylation levels of 25 tumor suppressor genes were analyzed using the methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) method. We found that a combination of six genes (TP73, CASP8, RARB, KLLN, GSTP1, and CHFR) could distinguish oral cancer from clinically diagnosed OPMDs with high diagnostic performance (area under the curve [AUC], 0.885; sensitivity, 77.8%; and specificity, 87.1%). Additionally, the panel comprised of the six methylated genes was validated in the test set. Furthermore, when compared with cytology testing, the panel could accurately detect oral cancer. The present methylated gene panel may serve as a novel biomarker for oral cancer.

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“…CELSR3 is closely related to the prognosis of cancer. CELSR3 is hypermethylated in oral squamous cell carcinoma (OSCC) and can be used as a potential biomarker for the diagnosis, prognosis, and treatment of OSCC (Khor et al, 2014). Karpathakis et al (2016) conducted a complete molecular identification of small intestinal neuroendocrine tumors (SINETs) and found that CELSR3 has a significant epigenetic mutation that might be a potential drug target.…”

Section: Discussionmentioning

confidence: 99%

CELSR3 mRNA expression is increased in hepatocellular carcinoma and indicates poor prognosis

Sha

et al. 2019

PeerJ

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Objective Hepatocellular carcinoma (HCC) is a disease that is associated with high mortality; currently, there is no curative and reliable treatment. Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3) is the key signaling molecule in the wingless and INT-1/planar cell polarity (WNT/PCP) pathway. This study aimed to elucidate the prognostic significance of CELSR3 in HCC patients. Methods The Cancer Genome Atlas (TCGA) database, the Cancer Cell Line Encyclopedia (CCLE) database and the Gene Expression Omnibus (GEO) database were used to analyze the expression of CELSR3 mRNA in HCC samples and cells. The relationship between CELSR3 mRNA and clinical features was assessed by the chi-square test. the diagnostic and predictive value of CELSR3 mRNA expression were analyzed using the receiver operating characteristic (ROC) curve. Kaplan–Meier curve and Cox regression analyses were performed to assess the prognostic value of CELSR3 mRNA in HCC patients. Finally, all three cohorts database was used for gene set enrichment analysis(GSEA) and the identification of CELSR3-related signal transduction pathways. Results The expression of CELSR3 mRNA was upregulated in HCC, and its expression was correlated with age (P = 0.025), tumor status (P = 0.022), clinical stage (P = 0.003), T classification (P = 0.010), vital status (P = 0.001), and relapse (P = 0.005). The ROC curve assessment indicated that CELSR3 mRNA expression has high diagnostic value in HCC and in the subgroup analysis of stage. In addition, the Kaplan-Meier curve and Cox analyses suggested that patients with high CELSR3 mRNA expression have a poor prognosis, indicating that CELSR3 mRNA is an independent prognostic factor for the overall survival of HCC patients. GSEA showed that GO somatic diversification of immune receptors, GO endonuclease activity, GO DNA repair complex and GO somatic cell DNA recombination, were differentially enriched in the meta-GEO cohort, the HCC cell line cohort and the TCGA cohort of the high CELSR3 mRNA expression phenotype. Conclusion Our results indicate that CELSR3 mRNA is involved in the progression of cancer and can be used as a biomarker for the prognosis of HCC patients.

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Screening of Differential Promoter Hypermethylated Genes in Primary Oral Squamous Cell Carcinoma

Cited by 11 publications

References 28 publications

Effect of CELSR3 on the Cell Cycle and Apoptosis of Hepatocellular Carcinoma Cells

Effect of CELSR3 on the Cell Cycle and Apoptosis of Hepatocellular Carcinoma Cells

Detecting Early-Stage Oral Cancer from Clinically Diagnosed Oral Potentially Malignant Disorders by DNA Methylation Profile

CELSR3 mRNA expression is increased in hepatocellular carcinoma and indicates poor prognosis

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