scholarly journals DNA Methylation Signatures Reveal the Diversity of Processes Remodeling Hepatocellular Carcinoma Methylomes

Hepatology ◽  
2021 ◽  
Author(s):  
Léa Meunier ◽  
Théo Z. Hirsch ◽  
Stefano Caruso ◽  
Sandrine Imbeaud ◽  
Quentin Bayard ◽  
...  
2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199296
Author(s):  
Juan Wang ◽  
Liu Yang ◽  
Yanjun Diao ◽  
Jiayun Liu ◽  
Jinjie Li ◽  
...  

Objective To evaluate the performance of a DNA methylation-based digital droplet polymerase chain reaction (ddPCR) assay to detect aberrant DNA methylation in cell-free DNA (cfDNA) and to determine its application in the detection of hepatocellular carcinoma (HCC). Methods The present study recruited patients with liver-related diseases and healthy control subjects. Blood samples were used for the extraction of cfDNA, which was then bisulfite converted and the extent of DNA methylation quantified using a ddPCR platform. Results A total of 97 patients with HCC, 80 healthy control subjects and 46 patients with chronic hepatitis B/C virus infection were enrolled in the study. The level of cfDNA in the HCC group was significantly higher than that in the healthy control group. For the detection of HCC, based on a cut-off value of 15.7% for the cfDNA methylation ratio, the sensitivity and specificity were 78.57% and 89.38%, respectively. The diagnostic accuracy was 85.27%, the positive predictive value was 81.91% and the negative predictive value was 87.20%. The positive likelihood ratio of 15.7% in HCC diagnosis was 7.40, while the negative likelihood ratio was 0.24. Conclusions A sensitive methylation-based assay might serve as a liquid biopsy test for diagnosing HCC.


2015 ◽  
Vol 7 (1) ◽  
pp. 15 ◽  
Author(s):  
Marie-Pierre Lambert ◽  
Pierre-Benoit Ancey ◽  
Davide Esposti ◽  
Marie-Pierre Cros ◽  
Athena Sklias ◽  
...  

2021 ◽  
Author(s):  
Yu-Xian Liu ◽  
Qian-Zhong Li ◽  
Yan-Ni Cao

Four genes related to DNA methylation were found to be independent prognostic factors and potential biomarkers for hepatocellular carcinoma.


2018 ◽  
Vol 145 (3) ◽  
pp. 675-684 ◽  
Author(s):  
Sophia Subat ◽  
Kaoru Mogushi ◽  
Mahmut Yasen ◽  
Takashi Kohda ◽  
Yuichi Ishikawa ◽  
...  

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12315
Author(s):  
Bing-Bing Shang ◽  
Jun Chen ◽  
Zhi-Guo Wang ◽  
Hui Liu

Background Hepatocellular carcinoma (HCC) is an inflammation-associated tumor involved in immune tolerance and evasion in the immune microenvironment. Heat shock proteins (HSPs) are involved in the occurrence, progression, and immune regulation of tumors. Therefore, HSPs have been considered potential therapeutic targets. Here, we aimed to elucidate the value of HSP family A (Hsp70) member 4 (HSPA4) in the diagnosis and predicting prognosis of HCC, and its relationship with immune cell infiltration, immune cell biomarkers, and immune checkpoints. Gene mutation, DNA methylation, and the pathway involved in HCC were also analyzed. Methods The gene expression omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were used to compare HSPA4 expression, and the results were confirmed by immunohistochemical staining of clinical samples. R package was used to analyze the correlation between HSPA4 and cancer stage, and to establish receiver operating characteristic (ROC) curve of diagnosis, time-dependent survival ROC curve, and a nomogram model. cBioPortal and MethSurv were used to identify genetic alterations and DNA methylation, and their effect on prognosis. The Tumor Immune Estimation Resource (TIMER) was used to analyze immune cell infiltration, immune cell biomarkers, and immune checkpoints. The STRING database was used to analyze protein–protein interaction network information. Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to investigate the functions of HSPA4 and its functional partner genes. Results Overexpression of HSPA4 was identified in 25 cancers. Overexpression of HSPA4 considerably correlated with cancer stage and alpha-fetoprotein (AFP) level in HCC. Patients with higher HSPA4 expression showed poorer prognosis. HSPA4 expression can accurately identify tumor from normal tissue (AUC = 0.957). The area under 1-, 3-, and 5-year survival ROCs were above 0.6. The HSPA4 genetic alteration rate was 1.3%. Among the 14 DNA methylation CpG sites, seven were related to the prognosis of HCC. HSPA4 was positively related to immune cell infiltration and immune checkpoints (PD-1 and CTLA-4) in HCC. The KEGG pathway enrichment analysis revealed HSPA4 enrichment in antigen processing and presentation together with HSPA8 and HSP90AA1. We verified the value of HSPA4 in the diagnosis and predicting prognosis of HCC. HSPA4 may not only participate in the occurrence and progression but also the immune regulation of HCC. Therefore, HSPA4 can be a potential diagnostic and prognostic biomarker and a therapeutic target for HCC.


Sign in / Sign up

Export Citation Format

Share Document