Differential DNA methylation analysis of SUMF2, ADAMTS5, and PXDN provides novel insights into colorectal cancer prognosis prediction in Taiwan

Su, Jing-Quan; Lai, Pin-Yu; Hu, P.; Hu, Je-Ming; Chang, Pi-Kai; Chen, Chaoyang; Wu, Jia-Jheng; Lin, Yu-Jyun; Sun, Chien‐An; Yang, Tsan; Hsu, Chih-Hsiung; Lin, Hua‐Ching; Chou, Yu‐Ching

doi:10.3748/wjg.v28.i8.825

Cited by 6 publications

(6 citation statements)

References 45 publications

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“…This study is also the first to analyze the effect of the PXDN methylation level on prognosis and report that hypermethylation of PXDN tends to represent longer patient survival times. As some studies have found that the PXDN methylation level is significant in pancreatic cancer ( 22 ) and colorectal tumors ( 23 ), we thus believe that the PXDN methylation level can be used as an independent predictor of tumor.…”

Section: Discussionmentioning

confidence: 81%

A systematic pan-cancer analysis of PXDN as a potential target for clinical diagnosis and treatment

Zhou

Sun

et al. 2022

Front. Oncol.

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Peroxidasin (PXDN), also known as vascular peroxidase-1, is a newly discovered heme-containing peroxidase; it is involved in the formation of extracellular mesenchyme, and it catalyzes various substrate oxidation reactions in humans. However, the role and specific mechanism of PXDN in tumor are unclear, and no systematic pan-cancer studies on PXDN have been reported to date. This study employed data from multiple databases, including The Cancer Genome Atlas and The Genotype-Tissue Expression, to conduct a specific pan-cancer analysis of the effects of PXDN expression on cancer prognosis. Further, we evaluated the association of PXDN expression with DNA methylation status, tumor mutation burden, and microsatellite instability. Additionally, for the first time, the relationship of PXDN with the tumor microenvironment and infiltration of fibroblasts and different immune cells within different tumors was explored, and the possible molecular mechanism of the effect was also discussed. Our results provide a comprehensive understanding of the carcinogenicity of PXDN in different tumors and suggest that PXDN may be a potential target for tumor immunotherapy, providing a new candidate that could improve cancer clinical diagnosis and treatment.

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Section: Discussionmentioning

confidence: 81%

A systematic pan-cancer analysis of PXDN as a potential target for clinical diagnosis and treatment

Zhou

Sun

et al. 2022

Front. Oncol.

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“…Genomic DNA samples were isolated from pathological tissue of CRC and adjacent normal tissue, and DNA bisulfite modification was performed according to the manufacturer’s instruction manual per a method described in a previous study [ 50 ].…”

Section: Methodsmentioning

confidence: 99%

“…The total volume of the reaction solution was 20 μL; the solution contained 9 μL of HotStart Taq Premix (RBC Bioscience, Taipei, Taiwan), 9 μL of pure water, 0.5 μL of 10 μM forward and reverse primers, and 1 μL of 10 μM bisulfite-modified DNA. The PCR cycling protocol reported in our previous study was adopted for MS-PCR [ 50 ].…”

Section: Methodsmentioning

confidence: 99%

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Significance of Hypermethylation of Tumor-Suppressor Genes PTGER4 and ZNF43 at CpG Sites in the Prognosis of Colorectal Cancer

Chen

Wu²,

Lin³

et al. 2022

IJMS

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The status of DNA methylation in primary tumor tissue and adjacent tumor-free tissue is associated with the occurrence of aggressive colorectal cancer (CRC) and can aid personalized cancer treatments at early stages. Tumor tissue and matched adjacent nontumorous tissue were extracted from 208 patients with CRC, and the correlation between the methylation levels of PTGER4 and ZNF43 at certain CpG loci and the prognostic factors of CRC was determined using the MassARRAY System testing platform. The Wilcoxon signed-rank test, a Chi-square test, and McNemar’s test were used for group comparisons, and Kaplan–Meier curves and a log-rank test were used for prediction. The hypermethylation of PTGER4 at the CpG_4, CpG_5, CpG_15, and CpG_17 tumor tissue sites was strongly correlated with shorter recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS) [hazard ratio (HR) = 3.26, 95% confidence interval (CI) = 1.38–7.73 for RFS, HR = 2.35 and 95% CI = 1.17–4.71 for PFS, HR = 4.32 and 95% CI = 1.8–10.5 for OS]. By contrast, RFS and PFS were significantly longer in the case of increased methylation of ZNF43 at the CpG_5 site of normal tissue [HR = 2.33, 95% CI = 1.07–5.08 for RFS, HR = 2.42 and 95% CI = 1.19–4.91 for PFS]. Aberrant methylation at specific CpG sites indicates tissue with aggressive behavior. Therefore, the differential methylation of PTGER4 and ZNF43 at specific loci can be employed for the prognosis of patients with CRC.

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“…Low density lipoprotein receptor-related protein 1-mediated endocytosis regulates extracellular activity of ADAMTS-5 in articular cartilage (Yamamoto et al, 2013(Yamamoto et al, , 2014. There are CpG islands within ADAMTS-5 promoter and DNA hypermethylation in ADAMTS-5 promoter is reportedly associated with increased invasiveness and poor survival in patients with colorectal cancer (Y. H. Kim et al, 2011;Li et al, 2018;Su et al, 2022). However, thus far there have been no reports concerning DNA methylation status in ADAMTS-5 promoter during OA development.…”

Section: Introductionmentioning

confidence: 99%

DNA demethylation of promoter region orchestrates SPI‐1‐induced ADAMTS‐5 expression in articular cartilage of osteoarthritis mice

Liu,

Lu,

et al. 2023

Journal Cellular Physiology

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Osteoarthritis (OA) is one of the most prevalent joint diseases in aged people and characterized by articular cartilage degeneration, synovial inflammation, and abnormal bone remodeling. Recent advances in OA research have clearly shown that OA development is associated with aberrant DNA methylation status of many OA‐related genes. As one of most important cartilage degrading proteases in OA, a disintegrin and metalloproteinase with thrombospondin motifs subtype 5 (ADAMTS‐5) is activated to mediate cartilage degradation in human OA and experimental murine OA models. The pathological factors and signaling pathways mediating ADAMTS‐5 activation during OA development are not well defined and have been a focus of intense research. ADAMTS‐5 promoter is featured by CpG islands. So far there have been no reports concerning the DNA methylation status in ADAMTS‐5 promoter during OA development. In this study, we sought to investigate DNA methylation status in ADAMTS‐5 promoter, the role of DNA methylation in ADAMTS‐5 activation in OA, and the underlying mechanisms. The potential for anti‐OA intervention therapy which is based on modulating DNA methylation is also explored. Our results showed that DNA methyltransferases 1 (Dnmt1) downregulation‐associated ADAMTS‐5 promoter demethylation played an important role in ADAMTS‐5 activation in OA, which facilitated SPI‐1 binding on ADAMTS‐5 promoter to activate ADAMTS‐5 expression. More importantly, OA pathological phenotype of mice was alleviated in response to Dnmt1‐induced DNA methylation of ADAMTS‐5 promoter. Our study will benefit not only for deeper insights into the functional role and regulation mechanisms of ADAMTS‐5 in OA, but also for the discovery of disease‐modifying OA drugs on the basis of ADAMTS‐5 via modulating DNA methylation status.

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Differential DNA methylation analysis of SUMF2, ADAMTS5, and PXDN provides novel insights into colorectal cancer prognosis prediction in Taiwan

Cited by 6 publications

References 45 publications

A systematic pan-cancer analysis of PXDN as a potential target for clinical diagnosis and treatment

A systematic pan-cancer analysis of PXDN as a potential target for clinical diagnosis and treatment

Significance of Hypermethylation of Tumor-Suppressor Genes PTGER4 and ZNF43 at CpG Sites in the Prognosis of Colorectal Cancer

DNA demethylation of promoter region orchestrates SPI‐1‐induced ADAMTS‐5 expression in articular cartilage of osteoarthritis mice

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