Bioinformatics analysis of DNMT1 expression and its role in head and neck squamous cell carcinoma prognosis

Cui, Jili; Zheng, Liduan; Zhang, Yuanyuan; Xue, Miaomiao

doi:10.1038/s41598-021-81971-5

Cited by 21 publications

(15 citation statements)

References 48 publications

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“…Recent studies showed that NSUN2 could promote tumour progression in HCC ( Sun et al, 2020 ) and gastric cancer ( Mei et al, 2020 ). Similar to our findings, Cui et al (2021) and Xue et al (2020b) found that DNMT1 played important roles in head and neck squamous cell carcinoma.…”

Section: Discussionsupporting

confidence: 93%

Uncovering the Association Between m5C Regulator-Mediated Methylation Modification Patterns and Tumour Microenvironment Infiltration Characteristics in Hepatocellular Carcinoma

Zhou

Chu

et al. 2021

Front. Cell Dev. Biol.

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Background: 5-Methylcytosine (m5C) plays essential roles in hepatocellular carcinoma (HCC), but the association between m5C regulation and immune cell infiltration in HCC has not yet been clarified.Methods: In this study, we analysed 371 patients with HCC from The Cancer Genome Atlas (TCGA) database, and the expression of 13 m5C regulators was investigated. Additionally, gene set variation analysis (GSVA), unsupervised clustering analysis, single-sample gene set enrichment analysis (ssGSEA), correlation analysis, and immunohistochemical (IHC) staining were performed.Results: Among the 371 patients, 41 had mutations in m5C regulators, the frequency of which was 11.26%. Compared with normal hepatic tissues, the expression of m5C regulators with copy number variations (CNVs) expansion was significantly higher than that in HCC tissues. Then, we identified three m5C modification patterns that had obvious tumour microenvironment (TME) cell infiltration characteristics. The prognostic analysis of the three major m5C modification subtypes showed that Cluster-2 had a clear survival advantage over the others. In addition, we found that DNMT1 was highly expressed in tumour tissues compared with normal tissues in a tissue microarray (TMA) and that it was positively correlated with many TME-infiltrating immune cells. High expression of the m5C regulator DNMT1 was related to a poor prognosis in patients with HCC. Furthermore, we developed three distinct Immu-clusters. Importantly, mRNAs related to the transcription of growth factor β (TGF-β)/EMT pathway were significantly up-regulated in Immu-cluster 2, indicating that this cluster is considered to be the immune rejection phenotype. Immu-cluster 3 showed elevated expression of mRNAs related to immune checkpoint genes.Conclusion: Our work revealed the association between m5C modification and immune regulators in the TME. These findings also suggest that DNMT1 has great potential as a prognostic biomarker and therapeutic target for HCC.

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Section: Discussionsupporting

confidence: 93%

Uncovering the Association Between m5C Regulator-Mediated Methylation Modification Patterns and Tumour Microenvironment Infiltration Characteristics in Hepatocellular Carcinoma

Zhou

Chu

et al. 2021

Front. Cell Dev. Biol.

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“…Recent studies showed that NSUN2 could promote tumour progression in HCC [37] and gastric cancer [38]. Similar to our ndings, Xue et al [39,40] found that DNMT1 played important roles in head and neck squamous cell carcinoma.…”

Section: Discussionsupporting

confidence: 91%

Uncovering of the Association Between m5C Regulator-Mediated Methylation Modification Patterns and Tumor Microenvironment Infiltration Characteristics in Hepatocellular Carcinoma

Zhou

Chu

et al. 2021

Preprint

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Background: 5-Methylcytosine (m5C) plays essential roles in hepatocellular carcinoma (HCC), but the association between m5C regulation and immune cell infiltration in HCC has not yet been clarified.Methods: In this study, we analysed 371 patients with HCC from The Cancer Genome Atlas (TCGA) database, and the expression of 13 m5C regulators was investigated. Additionally, gene set variation analysis (GSVA), unsupervised clustering analysis, single-sample gene set enrichment analysis (ssGSEA), correlation analysis, and immunohistochemical (IHC) staining were performed.Results: Among the 371 patients, 41 had mutations in m5C regulators, the frequency of which was 11.26%. Then, we identified three m5C modification patterns that had obvious tumour microenvironment (TME) cell infiltration characteristics. Cluster-1 had an immune rejection phenotype; Cluster-2 had an immunoinflammatory phenotype; and Cluster-3 had an immune desert phenotype. In addition, we found that DNMT1 was highly expressed in tumour tissues compared with normal tissues in a tissue microarray (TMA) and that it was positively correlated with many TME-infiltrating immune cells. High expression of the m5C regulator DNMT1 was related to a poor prognosis in patients with HCC. Furthermore, we developed three Immu-clusters that were consistent with the immune characteristics of the m5C methylation modification patterns. We also discovered differences in the levels of immune cells and expression of chemokines and cytokines among the three Immu-clusters.Conclusions: Our work revealed the association between m5C modification and immune regulators in the TME. These findings also suggest that DNMT1 has great potential as a prognostic biomarker and therapeutic target for HCC.

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“…In breast cancer [ 56 ], high DNMT1 expression is significantly associated with poor survival ( p < 0.05) using multivariate analysis. However, head and neck squamous cell carcinoma (HNSCC) with advanced-grade tumors have high DNMT1 expression that is associated with better overall survival [ 57 ]. In our study, 4-year MSS in stage IV patients revealed that high ac-DNMT1 protein level, not DNMT1 protein expression, is a significant independent prognostic marker in a multivariate analysis.…”

Section: Discussionmentioning

confidence: 99%

Acetylated DNMT1 Downregulation and Related Regulatory Factors Influence Metastatic Melanoma Patients Survival

Zhang

Bustos

Shoji

et al. 2021

Cancers

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The role of post-translational modifications (PTM) of the key epigenetic factor DNMT1 protein has not been well explored in cutaneous metastatic melanoma progression. The acetylated DNMT1 (ac-DNMT1) protein level was assessed using an anti-acetylated lysine antibody in a clinically annotated melanoma patient tumor specimen cohort. In this study, we showed that surgically resected tumors have significantly higher DNMT1 protein expression in metastatic melanoma (stage III metastasis n = 17, p = 0.0009; stage IV metastasis n = 164, p = 0.003) compared to normal organ tissues (n = 19). Additionally, reduced ac-DNMT1 protein levels were associated with melanoma progression. There was a significant inverse correlation between ac-DNMT1 and DNMT1 protein levels in stage IV metastatic melanoma (r = −0.18, p = 0.02, n = 164). Additionally, ac-DNMT1 protein levels were also significantly positively correlated with TIP60 (r = 0.6, p < 0.0001) and USP7 (r = 0.74, p < 0.0001) protein levels in stage IV metastatic melanoma (n = 164). Protein analysis in metastatic melanoma tumor tissues showed that with high ac-DNMT1 (p = 0.006, n = 59), or concurrent high ac-DNMT1 with low DNMT1 (p = 0.05, n = 27), or high TIP60 (p = 0.007, n = 41), or high USP7 (p = 0.01, n = 48) consistently showed better 4-year melanoma-specific survival (MSS). Multivariate Cox proportional hazard analysis showed that ac-DNMT1 level is a significant independent factor associated with MSS (HR, 0.994; 95% confidential interval (CI), 0.990–0.998; p = 0.002). These results demonstrated that low ac-DNMT1 levels may represent an important regulatory factor in controlling metastatic melanoma progression and a promising factor for stratifying aggressive stage IV metastasis.

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Bioinformatics analysis of DNMT1 expression and its role in head and neck squamous cell carcinoma prognosis

Cited by 21 publications

References 48 publications

Uncovering the Association Between m5C Regulator-Mediated Methylation Modification Patterns and Tumour Microenvironment Infiltration Characteristics in Hepatocellular Carcinoma

Uncovering the Association Between m5C Regulator-Mediated Methylation Modification Patterns and Tumour Microenvironment Infiltration Characteristics in Hepatocellular Carcinoma

Uncovering of the Association Between m5C Regulator-Mediated Methylation Modification Patterns and Tumor Microenvironment Infiltration Characteristics in Hepatocellular Carcinoma

Acetylated DNMT1 Downregulation and Related Regulatory Factors Influence Metastatic Melanoma Patients Survival

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