scholarly journals Identification of RASSF1A Promoter Hypermethylation as a Biomarker for Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Gang Xu ◽  
Xiaoxiang Zhou ◽  
Jiali Xing ◽  
Yao Xiao ◽  
Bao Jin ◽  
...  

Abstract Background: RAS association domain family protein 1A (RASSF1A) promoter hypermethylation is suggested to be linked to hepatocellular carcinoma (HCC), but the results remained controversial.Methods: We evaluated how RASSF1A promoter hypermethylation affects HCC risk and its clinicopathological characteristics through meta-analysis. Data on DNA methylation in HCC and relevant clinical data were also collected based on The Cancer Genome Atlas (TCGA) database to investigate the prognostic role of RASSF1A promoter hypermethylation in HCC.Results: Forty-four articles involving 4,777 individuals were enrolled in the pooled analyses. The RASSF1A promoter methylation rate was notably higher in the HCC cases than the non-tumor cases and healthy individuals, and was significantly related to hepatitis B virus (HBV) infection-positivity and large tumor size. Kaplan–Meier survival analysis revealed that HCC cases with RASSF1A promoter hypermethylation had worse outcomes. Receiver operating characteristic curves confirmed that RASSF1A promoter methylation may be a marker of HCC-related prognoses.Conclusions: RASSF1A promoter hypermethylation is a promising biomarker for the diagnosis of HCC from tissue and peripheral blood, and is an emerging therapeutic target against HCC.

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Gang Xu ◽  
Xiaoxiang Zhou ◽  
Jiali Xing ◽  
Yao Xiao ◽  
Bao Jin ◽  
...  

Abstract Background RAS association domain family protein 1A (RASSF1A) promoter hypermethylation is suggested to be linked to hepatocellular carcinoma (HCC), but the results remained controversial. Methods We evaluated how RASSF1A promoter hypermethylation affects HCC risk and its clinicopathological characteristics through meta-analysis. Data on DNA methylation in HCC and relevant clinical data were also collected based on The Cancer Genome Atlas (TCGA) database to investigate the prognostic role of RASSF1A promoter hypermethylation in HCC. Results Forty-four articles involving 4777 individuals were enrolled in the pooled analyses. The RASSF1A promoter methylation rate was notably higher in the HCC cases than the non-tumor cases and healthy individuals, and was significantly related to hepatitis B virus (HBV) infection-positivity and large tumor size. Kaplan–Meier survival analysis revealed that HCC cases with RASSF1A promoter hypermethylation had worse outcomes. Receiver operating characteristic curves confirmed that RASSF1A promoter methylation may be a marker of HCC-related prognoses. Conclusions RASSF1A promoter hypermethylation is a promising biomarker for the diagnosis of HCC from tissue and peripheral blood, and is an emerging therapeutic target against HCC.


2020 ◽  
Author(s):  
Gang Xu ◽  
Xiaoxiang Zhou ◽  
Jiali Xing ◽  
Yao Xiao ◽  
Bao Jin ◽  
...  

Abstract Background: RAS association domain family protein 1A (RASSF1A) promoter hypermethylation is suggested to be linked to hepatocellular carcinoma (HCC), but the results remained controversial. Methods: We evaluated how RASSF1A promoter hypermethylation affects HCC risk and its clinicopathological characteristics through meta-analysis. Data on DNA methylation in HCC and relevant clinical data were also collected based on The Cancer Genome Atlas (TCGA) database to investigate the prognostic role of RASSF1A promoter hypermethylation in HCC. Results: Forty-four articles involving 4,777 cases were enrolled in the pooled analyses. The RASSF1A promoter methylation rate was notably higher in the HCC cases than the non-tumor cases and healthy individuals, and was significantly related to hepatitis B virus (HBV) infection-positivity and large tumor size. Kaplan–Meier survival analysis revealed that HCC cases with RASSF1A promoter hypermethylation had worse outcomes. Receiver operating characteristic curves confirmed that RASSF1A promoter methylation may be a marker of HCC-related prognoses. Conclusions: RASSF1A promoter hypermethylation is a promising biomarker for the diagnosis of HCC from tissue and peripheral blood, and is an emerging therapeutic target against HCC.


2021 ◽  
Vol 49 (1) ◽  
pp. 030006052098154
Author(s):  
Xin Yuan ◽  
Yize Zhang ◽  
Zujiang Yu

Objective To investigate the association between microRNA-3615 (miR-3615) expression and the prognosis and clinicopathological features in patients with hepatocellular carcinoma (HCC). Methods We obtained clinicopathological and genomic data and prognostic information on HCC patients from The Cancer Genome Atlas (TCGA) database. We then analyzed differences in miR-3615 expression levels between HCC and adjacent tissues using SPSS software, and examined the relationships between miR-3615 expression levels and clinicopathological characteristics. We also explored the influence of miR-3615 expression levels on the prognosis of HCC patients using Kaplan–Meier survival curve analysis. Results Based on data for 345 HCC and 50 adjacent normal tissue samples, expression levels of miR-3615 were significantly higher in HCC tissues compared with adjacent tissues. MiR-3615 expression levels in HCC patients were negatively correlated with overall survival time and positively correlated with high TNM stage, serum Ki-67 expression level, and serum alpha-fetoprotein level. There were no significant correlations between miR-3615 expression and age, sex, and pathological grade. Conclusion MiR-3615 may be a promising new biomarker and prognostic factor for HCC.


2021 ◽  
Author(s):  
Jun Du ◽  
Jinguo Wang

Abstract Background: The expression and molecular mechanism of cysteine rich transmembrane module containing 1 (CYSTM1) in human tumor cells remains unclear. The aim of this study was to determine whether CYSTM1 could be used as a potential prognostic biomarker for hepatocellular carcinoma (HCC).Methods: We first demonstrated the relationship between CYSTM1 expression and HCC in various public databases. Secondly, Kaplan–Meier analysis and Cox proportional hazard regression model were performed to evaluate the relationship between the expression of CYSTM1 and the survival of HCC patients which data was downloaded in the cancer genome atlas (TCGA) database. Finally, we used the expression data of CYSTM1 in TCGA database to predict CYSTM1-related signaling pathways through bioinformatics analysis.Results: The expression level of CYSTM1 in HCC tissues was significantly correlated with T stage (p = 0.039). In addition, Kaplan–Meier analysis showed that the expression of CYSTM1 was significantly associated with poor prognosis in patients with early-stage HCC (p = 0.003). Multivariate analysis indicated that CYSTM1 is a potential predictor of poor prognosis in HCC patients (p = 0.036). The results of biosynthesis analysis demonstrated that the data set of CYSTM1 high expression was mainly enriched in neurodegeneration and oxidative phosphorylation pathways.Conclusion: CYSTM1 is an effective biomarker for the prognosis of patients with early-stage HCC and may play a key role in the occurrence and progression of HCC.


2020 ◽  
Author(s):  
Xuehui Peng ◽  
Yonggang He ◽  
Xiaobing Huang ◽  
Nan You ◽  
Huiying Gu ◽  
...  

Abstract Background: The tumorigenesis and development of hepatocellular carcinoma (HCC) is a process involving multiple factors. The COMMDs family proteins were reported to play important roles in various disease and cancers including HCC. We previously found COMMD7 acted as a HCC-promotion factor; however, further understanding on COMMD7 was needed. We conducted these bioinformatics analysis for the purpose of comprehensive understanding of the functional role of COMMD7 in HCC.Methods: The bioinformatics analysis of COMMD7 were launched by online platforms including KEGG, GEPIA, cBioportal, Gene Ontology and The Kaplan-Meier plotter. Data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were downloaded, and the data analysis and processing were conducted by RStudio (version 1.3.959) software.Results: The expression profile results of COMMD7 in TCGA and GTEx database suggested that COMMD7 expressed highly in liver tumor tissues and positively related with poorer prognosis (p<0.01); COMMD7 also contributed to the early development of HCC as its higher expression resulted in progression from stage I to stage III (p<0.01). Based on our previous studies, COMMD7 may target NF-κB signaling and CXCL10 to enhance the proliferation of hepatoma cells so that promoting the development of HCC. Conclusions:This study updates the current studies about the newly recognized roles of COMMD7 in the progression of HCC, summarizing the research progress and prospects of COMMD7 comprehensively, offering an outlook for the future investigation and targeted therapy of HCC.


Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1563
Author(s):  
Nathalie Théret ◽  
Fidaa Bouezzeddine ◽  
Fida Azar ◽  
Mona Diab-Assaf ◽  
Vincent Legagneux

The tumor microenvironment plays a major role in tumor growth, invasion and resistance to chemotherapy, however understanding how all actors from microenvironment interact together remains a complex issue. The tumor microenvironment is classically represented as three closely connected components including the stromal cells such as immune cells, fibroblasts, adipocytes and endothelial cells, the extracellular matrix (ECM) and the cytokine/growth factors. Within this space, proteins of the adamalysin family (ADAM for a disintegrin and metalloproteinase; ADAMTS for ADAM with thrombospondin motifs; ADAMTSL for ADAMTS-like) play critical roles by modulating cell–cell and cell–ECM communication. During last decade, the implication of adamalysins in the development of hepatocellular carcinoma (HCC) has been supported by numerous studies however the functional characterization of most of them remain unsettled. In the present review we propose both an overview of the literature and a meta-analysis of adamalysins expression in HCC using data generated by The Cancer Genome Atlas (TCGA) Research Network.


2021 ◽  
Author(s):  
Jihao Cai ◽  
Minglei Zhou ◽  
Jianxin Xu

Abstract Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. Due to its complex pathogenic factors, the prognosis of HCC is poor. Therefore, a credible prognostic biomarker is urgently needed for this disease. N6-methyladenosine (m6A) RNA methylation plays an important role in the tumorigenesis, progression and prognosis of many tumors. However, studies on the prognostic and therapeutic value of this modification in HCC are lacking.Case Presentation: The HCC RNA-seq profiles in The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases, including 421 LIHC and 440 LIRI samples respectively, were used in this study. The expressive distinction of 21 RNA methylation regulators between HCC and normal tissue were firstly assessed and SNRPC was obtained. Then the expression of SNRPC was validated as a risk factor for prognosis by Kaplan-Meier analysis and employed to establish a nomogram with T pathologic stage. By GSVA and GSEA analyses, we found SNRPC was mainly related to protein metabolism and immune process. Further, ESTIMATE, MCP-counter and single sample GSEA (ssGSEA) algorithm showed high-SNRPC expression group had lower stromal scores, a lower abundance of endothelial cells, fibroblasts and immune infiltration. Ultimately, Tumor Immune Dysfunction and Exclusion (TIDE) analysis exhibited high-SNRPC expression group showed non-response to immune checkpoint inhibitor therapy, especially to a PD-1 inhibitor.Conclusion: SNRPC could serve as valuable prognostic and immunotherapeutic marker in HCC. We provide here an accurate nomogram for clinical diagnosis using SNRPC as a biomarker.


2020 ◽  
Author(s):  
Jing Li ◽  
Xuehui Peng ◽  
Yonggang He ◽  
Xiaobing Huang ◽  
Nan You ◽  
...  

Abstract Background: The tumorigenesis and development of hepatocellular carcinoma (HCC) is a process involving multiple factors. The COMMDs family proteins were reported to play important roles in various disease and cancers including HCC. We previously found COMMD7 acted as a HCC-promotion factor; however, further understanding on COMMD7 was needed. We conducted these bioinformatics analysis for the purpose of comprehensive understanding of the functional role of COMMD7 in HCC.Methods: The bioinformatics analysis of COMMD7 were launched by online platforms including KEGG, GEPIA, cBioportal, Gene Ontology and The Kaplan-Meier plotter. Data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were downloaded, and the data analysis and processing were conducted by RStudio (version 1.3.959) software.Results: The expression profile results of COMMD7 in TCGA and GTEx database suggested that COMMD7 expressed highly in liver tumor tissues and positively related with poorer prognosis (p<0.01); COMMD7 also contributed to the early development of HCC as its higher expression resulted in progression from stage I to stage III (p<0.01). Based on our previous studies, COMMD7 may target NF-κB signaling and CXCL10 to enhance the proliferation of hepatoma cells so that promoting the development of HCC. Conclusions:This study updates the current studies about the newly recognized roles of COMMD7 in the progression of HCC, summarizing the research progress and prospects of COMMD7 comprehensively, offering an outlook for the future investigation and targeted therapy of HCC.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhihui Wang ◽  
Peihao Wen ◽  
Bowen Hu ◽  
Shengli Cao ◽  
Xiaoyi Shi ◽  
...  

Abstract Background Hepatocellular carcinoma (HCC) remains one of the most common malignant tumours worldwide. Therefore, the identification and development of sensitivity- genes as novel diagnostic markers and effective therapeutic targets is urgently needed. Dopamine and dopamine receptor D1 (DRD1) are reported to be involved in the progression of various cancers. However, the crucial role of DRD1 in HCC malignant activities remains unclear. Methods We enrolled 371 patients with liver hepatocellular carcinoma (LIHC) from The Cancer Genome Atlas (TCGA) to detect the expression and functions of DRD1. The Tumour Immune Estimation Resource (TIMER), UALCAN database, Kaplan–Meier plotter, cBioPortal database, and LinkedOmics database were utilized for the systematic investigation of DRD1 expression and related clinical features, coexpressed genes, functional pathways, mutations, and immune infiltrates in HCC. Results In this study, we determined that DRD1 expression was decreased in HCC tumour tissues versus normal tissues and that low DRD1 expression indicated a poor prognosis. The significance of DRD1 expression varied among different tumour samples. The somatic mutation frequency of DRD1 in the LIHC cohort was 0.3%. The biological functions of DRD1 were detected and validated, and DRD1 was shown to be involved in various functional activities, including metabolism, oxidation, mitochondrial matrix-related processes and other related signaling pathways. In addition, out study indicated that DRD1 had significant correlations with the infiltration of macrophages, B cells and CD+ T cells in HCC. Conclusions These findings demonstrated the rationality of the potential application of DRD1 function as a novel biomarker for HCC diagnosis and a therapeutic target for HCC treatment.


Author(s):  
Senbang Yao ◽  
Wenjun Chen ◽  
He Zuo ◽  
Ziran Bi ◽  
Xiuqing Zhang ◽  
...  

AbstractOxidative DNA damage is closely related to the occurrence and progression of cancer. Oxidative stress plays an important role in alcohol-induced hepatocellular carcinoma (HCC). Aldehyde dehydrogenase (ALDH) is a family of enzymes that plays an essential role in the reducing oxidative damage. However, how ALDHs family affects alcohol-related HCC remains obscure. We aimed to explore the correlation between the differential expression of ALDHs in patients with HCC and pathological features, as well as the relationship between ALDHs and prognosis, and finally analyze the possible mechanism of ALDHs in targeted therapy of HCC. The data of HCC were downloaded from The Cancer Genome Atlas (TCGA) database. This research explored the expression and prognostic values of ALDHs in HCC using Oncomine, UALCAN, Human Protein Atlas, cBioPortal, Kaplan–Meier plotter, GeneMANIA, Tumor Immune Estimation Resource, GEPIA databases, and WebGestalt. Low mRNA and protein expressions of ALDHs were found to be significantly associated with tumor grade and clinical cancer stages in HCC patients. In particular, the loss of ALDH expression is more obvious in Asians, and its effect on prognosis is far more significant than that in the White race. Our findings play an important role in the study of prognostic markers and anti-liver cancer therapeutic targets for the members of the ALDHs family, especially in patients with liver cancer in Asia.


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