Silencing NKD2 by Promoter Region Hypermethylation Promotes Esophageal Cancer Progression by Activating Wnt Signaling

Cao, Bowen; Yang, Weili; Jin, Yongshuai; Zhang, Meiying; He, Tao; Zhan, Qimin; Herman, James G.; Zhong, Guanglin; Guo, Mingzhou

doi:10.1016/j.jtho.2016.06.015

Cited by 33 publications

(30 citation statements)

References 57 publications

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“…DNA methylation‐based markers have emerged as clinically‐relevant disease markers due to their stability and tissue‐specificity . Previous studies have primarily focused on single candidate and emphasized more on their prognostic role in ESCC . Furthermore, these previous studies have additional shortcomings with respect to sample size analyzed and the inadequate representation of various stages of patients in the discovery and validation steps To overcome these drawbacks, in this current study, we have systematically and comprehensively identified and developed a methylation signature by using stringent criteria during the biomarker discovery phase.…”

Section: Discussionmentioning

confidence: 99%

“…[15][16][17][18] Previous studies have primarily focused on single candidate and emphasized more on their prognostic role in ESCC. [30][31][32] Furthermore, these previous studies have additional shortcomings with respect to sample size analyzed and the inadequate representation of various stages of patients in the discovery and validation steps 17,22,23 To overcome these drawbacks, in this current study, we have systematically and comprehensively identified and developed a methylation signature by using stringent criteria during the biomarker discovery phase. Considering the regional "spread" of methylation, we also took into account the methylation status of adjacent probes in a CpG island or DMR while selecting our candidates, thereby reducing the false positive hits and maximizing signal to noise ratio.…”

Section: Discussionmentioning

confidence: 99%

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A comprehensive methylation signature identifies lymph node metastasis in esophageal squamous cell carcinoma

Roy

Kandimalla

Sonohara

et al. 2018

Intl Journal of Cancer

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Treatment modalities in esophageal squamous cell carcinoma (ESCC) depend largely on lymph node metastasis (LNM) status. With suboptimal detection sensitivity of existing imaging techniques, we propose a methylation signature which identifies patients with LNM with greater accuracy. This would allow precise stratification of high-risk patients requiring more aggressive treatment from low-risk ESCC patients who can forego radical surgery. An unbiased genome-wide methylation signature for LNM detection was established from an initial in silico discovery phase. The signature was tested in independent clinical cohorts comprising of 249 ESCC patients. The prognostic potential of the methylation signature was compared to clinical variables including LNM status. A 10-probe LNM associated signature (LNAS) was developed using stringent bioinformatics analyses. The area under the curve values for LNAS risk scores were 0.81 and 0.88 in the training and validation cohorts respectively, in association with lymphatic vessel invasion and tumor stage. High LNAS risk-score was also associated with worse overall survival [HR (95% CI) 3 (1.8-4.8), p < 0.0001 training and 3.9 (1.5-10.2), p = 0.001 validation cohort]. In conclusion, our novel methylation signature is a powerful biomarker that identifies LNM status robustly and is also associated with worse prognosis in ESCC patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A comprehensive methylation signature identifies lymph node metastasis in esophageal squamous cell carcinoma

Roy

Kandimalla

Sonohara

et al. 2018

Intl Journal of Cancer

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“…Western blot was performed as described previously [5]. Antibodies were diluted according to manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

“…While, aberrant epigenetic changes were found frequently in human HCC. DNA methylation was found involved in various cancer-related signaling pathways, including Wnt, p53, and TGF-β signaling [5-9]. …”

Section: Introductionmentioning

confidence: 99%

ZNF545 suppresses human hepatocellular carcinoma growth by inhibiting NF-kB signaling

Yang

Zhang

et al. 2017

Genes Cancer

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Hepatocellular carcinoma (HCC) is one of the most common cancers and the second leading cause of cancer related death worldwide. ZNF545 is located in the chromosome 19q13.13, which is frequent loss of heterozygosity in human astrocytoma. Methylation of ZNF545 was found frequently in a few kinds of cancers. While the function of ZNF545 in human HCC remains unclear. The purpose of this study is to explore the function and mechanism of ZNF545 in human HCC. Restoration of ZNF545 expression suppressed cell proliferation, migration and invasion, induced G1/S arrest and apoptosis in SNU449 and Huh7 cells. Further study suggested that ZNF545 suppressed HCC cell growth by inhibiting NF-kB signaling. These results were further validated by siRNA knocking down technique in ZNF545 highly expressed HXBF344 cells. In vivo, ZNF545 suppressed tumor growth in SNU449 cell xenograft mice. In conclusion, ZNF545 suppresses human HCC growth by inhibiting NF-kB signaling.

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“…Moreover, diet can cause profound changes in the epigenome, leading to human disease [9]. Aberrant DNA methylation has been reported in genes involved in cell cycle, DNA damage repair, Wnt, TGF-β, and NF-κB pathways [12,13].…”

Section: Introductionmentioning

confidence: 99%

Epigenetic silencing of IGFBPL1 promotes esophageal cancer growth by activating PI3K-AKT signaling

Yingge

Zhang

et al. 2020

Clin Epigenet

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Background: There are seven insulin-like growth factor binding proteins (IGFBPs) that bind insulin-like growth factors (IGFs). IGFBP like protein1 (IGFBPL1) is a new member of this family. The function and mechanism of IGFBPL1 in esophageal cancer remains to be elucidated. Methods: Eight esophageal cancer cell lines, 114 cases of esophageal dysplasia, and 501 cases of primary esophageal cancer samples were examined in this study. Methylation-specific polymerase chain reaction (MSP), immunohistochemistry, Western blot, flow cytometry, RNA interference assay, and xenograft mouse models were employed. Results: The expression of IGFBPL1was lost and complete methylation was found in KYSE150 and KYSE410 cells. Reduced expression and partial methylation of IGFBPL1 was found in Bic1, KYSE140, KYSE450, KYSE520, and COLO680N cells. High expression and unmethylation was detected in KYSE510 cells. Restoration of IGFBPL1 expression was found in KYSE150 and KYSE410 cells and the expression of IGFBPL1 was increased in Bic1, KYSE140, KYSE450, KYSE520, and COLO680N cells, after 5-AZA-2′-deoxycytidine treatment. IGFBPL1 was methylated in 47.3% (53/114) of esophageal dysplasia and 49.1% (246/501) of human primary esophageal squamous cell carcinoma (ESCC). Methylation of IGFBPL1 was significantly associated with TNM stage (p = 0.012), and tumor size (p = 0.009). IGFBPL1 inhibited esophageal cancer cell clonal formation and proliferation and induced cell apoptosis and G1/S phase arrest. Further study found that IGFBPL1 is involved in PI3K-AKT signaling and IGFBPL1 suppressed human ESCC xenografts growth in mice. Conclusion: IGFBPL1 suppresses esophageal cancer cell growth by inhibiting PI3K-AKT signaling in vitro and in vivo. IGFBPL1 is a novel tumor suppressor in human esophageal cancer.

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Silencing NKD2 by Promoter Region Hypermethylation Promotes Esophageal Cancer Progression by Activating Wnt Signaling

Abstract: NKD2 is frequently methylated in human esophageal cancer, and the expression of NKD2 is regulated by promoter region methylation. NKD2 suppresses esophageal cancer progression by inhibiting Wnt signaling both in vitro and in vivo.

Cited by 33 publications

References 57 publications

A comprehensive methylation signature identifies lymph node metastasis in esophageal squamous cell carcinoma

A comprehensive methylation signature identifies lymph node metastasis in esophageal squamous cell carcinoma

ZNF545 suppresses human hepatocellular carcinoma growth by inhibiting NF-kB signaling

Epigenetic silencing of IGFBPL1 promotes esophageal cancer growth by activating PI3K-AKT signaling

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