Hypomethylation of long interspersed nuclear element‐1 promoter is associated with poor outcomes for curative resected hepatocellular carcinoma

Gao, Xudong; Qu, Jing; Chang, Xiujuan; Lu, Yinying; Bai, Wenlin; Wang, Hong; Xu, Zhongxian; An, Lihui; Wang, Chunping; Zeng, Zhen; Yang, Yongping

doi:10.1111/liv.12264

Cited by 40 publications

(37 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the significant difference between adjacent non-tumor tissues and normal liver tissues was not observed in this study, and hypermethylation of TRIM58 appeared in HCC tissues, but not in adjacent non-tumor tissues and normal liver tissues. The results indicated that hypermethylation of TRIM58 (>10%) was one of the specific events associated with tumorigenesis rather than other benign pathological processes, such as inflammation and cirrhosis (18).…”

Section: Discussionmentioning

confidence: 94%

Aberrant methylation of TRIM58 in hepatocellular carcinoma and its potential clinical implication

et al. 2016

View full text Add to dashboard Cite

Abstract. TRIM58 (tripartite motif containing 58) has been reported as a novel methylated gene in hepatocellular carcinoma (HCC) by methylation microarrays. However, its associations with mRNA expression and clinicopathological characteristics have not been evaluated. In this study, we explored the potential clinical implications of TRIM58 methylation in HCC. We analyzed the methylation level of TRIM58 in 181 HCC tissues, 172 matched adjacent non-tumor tissues and 13 normal liver tissues using methylation-sensitive restriction enzyme based quantitative PCR and bisulfite genomic sequencing. Further, the mRNA expression level of TRIM58 was measured in 46 paired HCC and adjacent non-tumor tissues by quantitative real-time PCR. Moreover, the relationship between TRIM58 methylation and mRNA expression, the clinicopathological features, as well as prognostic value were evaluated. The results showed that TRIM58 methylation was significantly higher in HCC tissues compared with adjacent non-tumor tissues and normal liver tissues (both p<0.0001). Using 10% as the cut-off value, hypermethylation of TRIM58 was specific in HCC tissues (28.18%, 51/181), with a tendency to correlate with unfavorable disease-free survival (p=0.047). Moreover, TRIM58 expression was significantly decreased in HCC tissues compared with adjacent non-tumor tissues (p<0.0001), and showed a negative association with DNA methylation (p=0.015, r s = -0.260). Our data indicate that TRIM58 methylation is a common event in HCC and may contribute to downregulation of its mRNA expression. Furthermore, hypermethylation of TRIM58 tends to be associated with worse DFS after hepatectomy. However, the potential clinical application of TRIM58 need to be further investigated.

show abstract

Section: Discussionmentioning

confidence: 94%

Aberrant methylation of TRIM58 in hepatocellular carcinoma and its potential clinical implication

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Therefore, stepwise progression of methylation alterations may take place during the development of HCC. Many studies have reported that DNA hypomethylation in tumors is associated with aggressive tumors showing rapid growth [16,17]. We previously reported that the number of genes with hypermethylation increased with tumor progression [18].…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Profiling of DNA Methylation and Tumor Progression in Human Hepatocellular Carcinoma

Nishida

Nishimura²,

Nakai³

et al. 2014

Dig Dis

View full text Add to dashboard Cite

Objective: To clarify the progression pattern of abnormal DNA methylation during the development of hepatocellular carcinoma (HCC) using a comprehensive methylation assay. Methods: We used an Infinium HumanMethylation450 BeadChip array that can analyze >485,000 CpG sites distributed throughout the genome for a comprehensive methylation study of 117 liver tissues consisting of 59 HCC and 58 noncancerous livers. Altered DNA methylation patterns during tumor progression were also analyzed. Results: We identified 38,330 CpG sites with significant differences in methylation levels between HCCs and noncancerous livers (DM-CpGs) using strict criteria. Of the DM-CpGs, 92% were hypomethylated and only 3,051 CpGs (8%) were hypermethylated in HCC. The DM-CpGs were more prevalent within intergenic regions with isolated CpGs. In contrast, DM-CpGs that were hypermethylated in HCC were predominantly located within promoter regions and CpG islands (p < 0.0001). The association between methylation profiles of DM-CpGs and tumor size was statistically significant, especially in hepatitis C virus (HCV)-positive cases (p = 0.0001). Conclusions: We clarified the unique characteristics of DM-CpGs in human HCCs. The stepwise progression of alterations in DNA methylation was a common feature of HCV-related hepatocarcinogenesis.

show abstract

“…It has been shown that a hypomethylation of the CpG site of LINE-1 at the promoter region, particularly at CpG site seven, which is the number 172 nucleotide of LINE-1 promoter (gene bank: X58075), is associated with the LINE-1 re-expression [27]. Therefore, the results of methylation specific polymerase chain reaction (PCR) (MSP), which detects specific methylation status at this CpG site, would indirectly indicate the expression status of the LINE-1 gene in a tested sample.…”

Section: Dna Methylation Analysismentioning

confidence: 99%

Hypomethylation of Long Interspersed Nuclear Element-1 is Involved in the Early Tumorigenesis of Hepatocellular Carcinoma

Piao¹,

Wang²,

Zhang³

et al. 2014

J Interdiscipl Histopathol

View full text Add to dashboard Cite

Objective: Hypomethylation of long interspersed nucleotide elements 1 (LINE-1) promoter has been reported in many cancer types including pancreatic endocrine tumors, colon cancers, and stomach carcinomas. Hypomethylation of LINE-1 is also frequently observed in hepatocellular carcinoma (HCC). However, it still unknown how LINE-1 is involved in the hepatocarcinogenesis. Methods: The level of LINE-1 promoter methylation in 28 HCC was detected by a methylation specific polymerase chain reaction (MSP) at CpG site seven of LINE-1 promoter region (gene bank: X58075). A fractional allelic loss (FAL) of these tumors was evaluated by a combination of loss of heterozygosity with microsatellite markers D4S1545, D4S2920, D8S264, D8S1752, D16S498, D16S514, and p53. The associations between the level of LINE-1 hypomethylation status and the clinico-pathological parameters were finally observed. The clinicopathological parameters were included hepatitis B virus (HBV) status, cirrhosis, tumor size, tumor differentiation and FAL. Results: High level of hypomethylation of LINE-1 promoter was found both in the advanced tumors (>3 cm), (7/18, 39%) and in the early tumors (<3 cm), (6/10, 60%). Moreover, the high level of deoxyribonucleic acid hypomethylation at the LINE-1 was found in both poorly differentiated tumors (8/13, 61.5%) and well-differentiated tumors (5/15, 33.3%). The mean value of FAL in 28 HCCs was 0.535. All cases were divided according to FAL score: Low FAL (FAL < 0.535) and high FAL (FAL > 0.535). There were 41% (7/17) tumors with a high level of hypomethylation in the low FAL group and 54.5% (6/11) tumors with a high level of hypomethylation in the high FAL group. No associations between the level of hypomethylation of LINE-1 and HBV infection, age, sex, and cirrhosis were found. Conclusions: These results are strongly suggested that the hypomethylation of LINE-1 plays a role in the hepatocarcinogenesis; moreover, the hypomethylation of LINE-1 occurs not only in the progression of HCC, but also in the early stage of HCC tumorigenesis.

show abstract

Hypomethylation of long interspersed nuclear element‐1 promoter is associated with poor outcomes for curative resected hepatocellular carcinoma

Cited by 40 publications

References 38 publications

Aberrant methylation of TRIM58 in hepatocellular carcinoma and its potential clinical implication

Aberrant methylation of TRIM58 in hepatocellular carcinoma and its potential clinical implication

Genome-Wide Profiling of DNA Methylation and Tumor Progression in Human Hepatocellular Carcinoma

Hypomethylation of Long Interspersed Nuclear Element-1 is Involved in the Early Tumorigenesis of Hepatocellular Carcinoma

Contact Info

Product

Resources

About