An aberrant DNA methylation signature for predicting hepatocellular carcinoma

Zhang, Renhua; Li, Yafei; Yu, Hao; Liu, Lin; Zhu, Changhao; Zuo, Shi; Chen, Zili

doi:10.21037/atm-20-7804

Cited by 7 publications

(6 citation statements)

References 61 publications

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“…A growing body of evidence has suggested that DNA methylation is strongly correlated with gene alteration in cancers ( Wang et al, 2020 ; Zhang et al, 2020 ). Therefore, we searched the methylation profiles of BRAF and its downstream genes in TCGA cancers by using the GSCALite database ( Figures 1D,E ).…”

Section: Resultsmentioning

confidence: 99%

Spectrum of BRAF Aberrations and Its Potential Clinical Implications: Insights From Integrative Pan-Cancer Analysis

Peng

et al. 2022

Front. Bioeng. Biotechnol.

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B-Raf proto-oncogene serine/threonine-protein kinase (BRAF) is frequently altered in multiple cancer types, and BRAF V600 mutations act as a prime target for precision therapy. Although emerging evidence has investigated the role of BRAF, the comprehensive profiling of BRAF expression, alteration and clinical implications across various cancer types has not been reported. In this study, we used the TCGA dataset, covering 10,967 tumor samples across 32 cancer types, to analyze BRAF abnormal expression, DNA methylation, alterations (mutations and amplification/deletion), and their associations with patient survival. The results showed that BRAF expression, alteration frequency, mutation site distribution, and DNA methylation patterns varied tremendously among different cancer types. The expression of BRAF was found higher in PCPG and CHOL, and lower in TGCT and UCS compared to normal tissues. In terms of pathological stages, BRAF expression was significantly differentially expressed in COAD, KIRC, LUSC, and OV. The methylation levels of BRAF were significantly lower in LUSC, HNSC, and UCEC compared to normal tissue. The expression of BRAF and downstream gene (ETS2) was negatively correlated with methylation levels in various cancers. The overall somatic mutation frequency of BRAF was 7.7% for all cancer samples. Most fusion transcripts were found in THCA and SKCM with distinct fusion patterns. The majority of BRAF mutations were oncogenic and mainly distributed in the Pkinase_Tyr domain of THCA, SKCM, COADREAD, and LUAD. The BRAF mutations were divided into five levels according to the clinical targeted therapy implication. The results showed level 1 was mainly distributed in SKCM, COADREAD, and LUAD, while level 3B in THCA. The overall BRAF CNV frequency was about 42.7%, most of which was gain (75.9%), common in GBM, TGCT, and KIRP. In addition, the forest plot showed that increased BRAF expression was associated with poor patient overall survival in LIHC, OV, and UCEC. Taken together, this study provided a novel insight into the full alteration spectrum of BRAF and its implications for treatment and prognosis.

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Section: Resultsmentioning

confidence: 99%

Spectrum of BRAF Aberrations and Its Potential Clinical Implications: Insights From Integrative Pan-Cancer Analysis

Peng

et al. 2022

Front. Bioeng. Biotechnol.

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“…Liver cancer, with a high death rate and poor 5-years survival, is considered to be one of the most malignant cancers in the world (Feng et al, 2020). The factors leading to liver cancer are as follows: infection of hepatitis B virus (HBV), infection of hepatitis C virus (HCV), alcohol abuse, and alternations of genetic and epigenetic events (Zhang et al, 2020b). There are many strategies to treat liver cancer, such as chemotherapy, radiotherapy, molecular targeted therapy, surgical resection, and liver transplantation (Petrowsky et al, 2020).…”

Section: Liver Cancermentioning

confidence: 99%

Alantolactone: A Natural Plant Extract as a Potential Therapeutic Agent for Cancer

et al. 2021

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Alantolactone (ALT) is a natural compound extracted from Chinese traditional medicine Inula helenium L. with therapeutic potential in the treatment of various diseases. Recently, in vitro and in vivo studies have indicated cytotoxic effects of ALT on various cancers, including liver cancer, colorectal cancer, breast cancer, etc. The inhibitory effects of ALT depend on several cancer-associated signaling pathways and abnormal regulatory factors in cancer cells. Moreover, emerging studies have reported several promising strategies to enhance the oral bioavailability of ALT, such as combining ALT with other herbs and using ALT-entrapped nanostructured carriers. In this review, studies on the anti-tumor roles of ALT are mainly summarized, and the underlying molecular mechanisms of ALT exerting anticancer effects on cells investigated in animal-based studies are also discussed.

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“…There is a negative correlation between DNA methylation and gene expression levels ( Gensous et al, 2020 ; Kronfol et al, 2020 ; Wang et al, 2020b ; Zhang et al, 2020 ). In our results, the DNA methylation of ALKBH1/2/4/5 and FTO was decreased in HCC patients compared with healthy persons ( p < 0.05) ( Fig.…”

Section: Resultsmentioning

confidence: 99%

The bioinformatics and experimental analysis of AlkB family for prognosis and immune cell infiltration in hepatocellular carcinoma

Peng

Yan

2021

PeerJ

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Background Serving as N6-methyladenosine demethylases, the AlkB family is involved in the tumorigenesis of hepatocellular carcinoma (HCC). However, the molecular profiles and clinical values of the AlkB family in HCC are not well known. Methods Several bioinformatics tools and in vitro experiments were used to identify the immune-related profiles and prognostic values of AlkB family in HCC. Results In this study expression levels of ALKBH1/2/3/4/7 were all remarkably increased in HCC tissues when compared with normal tissues. Quantitative PCR (qPCR) and immunohistochemistry were used to validate the expression of AlkB family members in HCC tissues and normal liver tissues. In addition, high expression levels of ALKBH4 were negatively correlated with overall survival (OS) and disease-free survival (DFS) in patients with HCC. Increased ALKBH4 was also associated with pathological stage in HCC patients. The molecular profiles of AlkB family in HCC were mainly associated with peptidyl-serine modification, peptidyl-tyrosine modification, regulation of metal ion transport, etc. Furthermore, tumor-infiltrating immune cell analysis indicated that ALKBH1/2/3/4/5/6/7/8 and FTO were related to the infiltration of different immune cell, such as CD8+ T cells, macrophages, neutrophils, dendritic cells and CD4+ T cells. We also discovered that the methylation levels of ALKBH1/2/4/5/6/8 and FTO were remarkably reduced in HCC tissues. Conclusions Collectively, our findings may deepen the understanding of specific molecular profiles of the AlkB family in HCC pathology. In particular, ALKBH4 could serve as a promising prognostic candidate for treating HCC, and these results might potentiate the development of more reliable therapeutic strategies for patients with HCC.

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An aberrant DNA methylation signature for predicting hepatocellular carcinoma

Cited by 7 publications

References 61 publications

Spectrum of BRAF Aberrations and Its Potential Clinical Implications: Insights From Integrative Pan-Cancer Analysis

Spectrum of BRAF Aberrations and Its Potential Clinical Implications: Insights From Integrative Pan-Cancer Analysis

Alantolactone: A Natural Plant Extract as a Potential Therapeutic Agent for Cancer

The bioinformatics and experimental analysis of AlkB family for prognosis and immune cell infiltration in hepatocellular carcinoma

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