Identification by TCGA database search of five genes that are aberrantly expressed and involved in hepatocellular carcinoma potentially via DNA methylation changes

Abstract

Background Various treatments for hepatocellular carcinoma (HCC) are utilized in clinical practice; however, the prognosis is still poor on account of high recurrence rates. DNA methylation levels of CpG islands around promoters (promoter CpGis) inversely regulate gene expression and closely involved in carcinogenesis. As a new strategy, several chemicals globally inhibiting DNA methylation have been developed aiming at reducing DNA methylation levels and maintaining the expression of tumor suppressor genes. On the other hand, since these drugs nonspecifically modify DNA methylation, they can cause serious adverse effects. In order to ameliorate the methods by targeting specific CpGs, information of cancer-related genes that are regulated by DNA methylation is required. Methods We searched candidate genes whose expressions were regulated by DNA methylation of promoter CpGi and which are involved in HCC cases. To do so, we first identified genes whose expression were changed in HCC by comparing gene expressions of 371 HCC tissues and 41 non-tumor tissues using the Cancer Genome Atlas (TCGA) database. The genes were further selected for poor prognosis by log-rank test of Kaplan-Meier plot and for cancer relevance by Pubmed search. Expression profiles of upregulated genes in HCC tissues were assessed by Gene Ontology (GO) analysis. Finally, using DNA methylation data of TCGA database, we selected genes whose promoter DNA methylation levels were inversely correlated with gene expression. Results We found 115 genes which were significantly up- or downregulated in HCC tissues and were associated with poor prognosis and cancer relevance. The upregulated genes were significantly enriched in cell division, cell cycle, and cell proliferation. Among the upregulated genes in HCC, we identified hypomethylation of CpGis around promoters of FANCB , KIF15 , KIF4A , ERCC6L , and UBE2C . In addition, TCGA data showed that the tumor suppressor gene P16 is unexpectedly overexpressed in many types of cancers. Conclusions We identified five candidate genes whose expressions were regulated by DNA methylation of promoter CpGi and associate with cancer cases and poor prognosis in HCC. Modification of site-specific DNA methylation of these genes enables a different approach for HCC treatment with higher selectivity and lower adverse effects.

The Expression and Role Analysis of Methylation-Regulated Differentially Expressed Gene UBE2C in Pan-Cancer, Especially for HGSOC

“…Another genome-wide DNA methylation analysis in nonalcoholic steatohepatitis-related hepatocellular carcinomas found both hypomethylation of UBE2C promoters and UBE2C upregulation in hepatocellular carcinomas [29]. Recently, bioinformatics analyses have also discovered a UBE2C overexpression-hypomethylation correlation in hepatocellular carcinoma [30,31]. In agreement with the previous studies, our data found significant DNA hypomethylation of UBE2C in CHOL, KIRC, and PCPG tumor tissues and a negative correlation between the methylation levels of UBE2C and its expression levels in multiple cancer types.…”

Sofosbuvir-Upregulated Genes Facilitate The Development of Hepatocellular Carcinoma

“…Top-ranked genes were selected for further investigation (Table S1). To further evaluate the clinical meaning of the upregulated genes in patients with HCC, the TCGA database, one of the largest genomic databases available for various cancer types that can be downloaded from an open-access resource, [43][44][45] is used for analysis ( Table 1). The TCGA data analysis showed that several genes upregulated by SOF in OR-6 cells, including PHOSPHO2, KLHL23, TSNAX-DISC1, TRIM39 and RPP21, were signi cantly higher in HCC tumor tissues than in non-tumor tissues ( Table 1), suggesting that PHOSPHO2, KLHL23, TSNAX-DISC1, TRIM39 and RPP21 were associated with the development of HCC.…”

INK4 cyclin-dependent kinase inhibitors as potential prognostic biomarkers and therapeutic targets in hepatocellular carcinoma

“…The efficacy of immunotherapy requires sufficient immune infiltration into the tumor microenvironment and depends on the expression of immune checkpoint molecules [ 41 , 42 ]. Recent studies have reported that CDKN2A is closely associated with immune infiltration of HCC [ 12 , 43 , 44 ]. However, the relationship between other INK4 family members and HCC is unclear.…”