Background: DNA methylation is one of most frequently occurring molecular behaviours that occurs early during the complicated carcinogenesis process of hepatocellular carcinoma (HCC).
Methods: In this study, 348 samples were collected from The Cancer Genome Atlas (TCGA) database and analysed to mine the specific DNA methylation sites that affect the prognosis of HCC patients.
Results: The 10699 selected CpG sites (CpGs) that were markedly correlated with patient prognosis were used for consistent clustering of the samples into 7 subgroups, and the samples in each subgroup varied in terms of race, age, tumour stage, receptor status, histological type, metastasis status and patient prognosis. In addition, the level of methylation sites in each subgroup were calculated, and 119 methylation sites (corresponding to 105 genes) were screened as the intra-subgroup-specific methylation sites. Moreover, genes in the corresponding promoter regions in which the above specific methylation sites were located were subjected to signalling pathway enrichment analysis, and it was discovered that these genes were enriched in the bio-logical pathways that were reported to be closely correlated with HCC. Additionally, the subsequent transcription factor enrichment analysis revealed that these genes were mainly enriched in the transcription factor KROX. A prognosis prediction mod-el for HCC patients was constructed using the naive Bayesian classification model, and the training and test datasets were used for independent verification and testing.
Conclusions: This classification method based on specific DNA methylation sites can well reflect the heterogeneity of HCC tissues and contributes to developing individualized treatments and accurately predicting patient prognosis.

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This is a list of supplementary files associated with this preprint. Click to download.
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Posted 09 Apr, 2020
Posted 09 Apr, 2020
Background: DNA methylation is one of most frequently occurring molecular behaviours that occurs early during the complicated carcinogenesis process of hepatocellular carcinoma (HCC).
Methods: In this study, 348 samples were collected from The Cancer Genome Atlas (TCGA) database and analysed to mine the specific DNA methylation sites that affect the prognosis of HCC patients.
Results: The 10699 selected CpG sites (CpGs) that were markedly correlated with patient prognosis were used for consistent clustering of the samples into 7 subgroups, and the samples in each subgroup varied in terms of race, age, tumour stage, receptor status, histological type, metastasis status and patient prognosis. In addition, the level of methylation sites in each subgroup were calculated, and 119 methylation sites (corresponding to 105 genes) were screened as the intra-subgroup-specific methylation sites. Moreover, genes in the corresponding promoter regions in which the above specific methylation sites were located were subjected to signalling pathway enrichment analysis, and it was discovered that these genes were enriched in the bio-logical pathways that were reported to be closely correlated with HCC. Additionally, the subsequent transcription factor enrichment analysis revealed that these genes were mainly enriched in the transcription factor KROX. A prognosis prediction mod-el for HCC patients was constructed using the naive Bayesian classification model, and the training and test datasets were used for independent verification and testing.
Conclusions: This classification method based on specific DNA methylation sites can well reflect the heterogeneity of HCC tissues and contributes to developing individualized treatments and accurately predicting patient prognosis.

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7
This is a list of supplementary files associated with this preprint. Click to download.
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