Integrated Proteogenomic Characterization of HBV-Related Hepatocellular Carcinoma

Gao, Qiang; Zhu, Hongwen; Dong, Liangqing; Shi, Weiwei; Chen, Ran; Song, Zhijian; Huang, Chen; Li, Junqiang; Dong, Xiaowei; Zhou, Yanheng; Liu, Qian; Ma, Li; Wang, Xiaoying; Zhou, Ji; Liu, Yansheng; Boja, Emily S.; Robles, Ana I.; Ma, Wanli; Wang, Pei; Li, Yize; Li, Ding; Wen, Bo; Zhang, Bing; Rodriguez, Henry; Gao, Daming; Zhou, Hu; Fan, Jia

doi:10.1016/j.cell.2019.08.052

Cited by 668 publications

(582 citation statements)

References 83 publications

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“…Globally, liver cancer is the fourth leading cause of cancer-related deaths, with the sixth highest incidence (1). HCC accounts for about 80% of all cases of primary liver cancer, most of which occur in patients with chronic diseases such as hepatitis B virus (HBV), hepatitis C virus (HCV) and alcoholism (25,26). The increase in deaths caused by HCC is a growing concern.…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of Novel Biomarkers for Diagnosis and Prognosis of Hepatocellular Carcinoma

Bao

Huang

et al. 2020

Front. Oncol.

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Introduction: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide due to poor survival outcome. Thus, there is an urgent need to identify effective biomarkers for early diagnosis and prognosis prediction. Methods: A total of 389 differentially expressed genes (DEGs) between HCC samples and normal were selected based on the Robust Rank Aggregation (RRA) method. We combined DEGs expression and clinical traits to construct a gene co-expression network through WGCNA. Forty hub genes were selected from the key module. Among them, YWHAB, PPAT, NOL10 were eventually identified as prognostic biomarkers using multivariate Cox regression model. Biomarkers expression pattern was investigated by informatic analysis and verified by RNA-seq of 32 patients with HCC. DiseaseMeth 2.0, MEXPRESS, and Tumor Immune Estimation Resource (TIMER) were used to assess the methylation and immune status of biomarkers. GSVA, CCK8, colony formation assay, Edu imaging kit, wound-healing assay, and xenograft tumor model were utilized to investigate the effects of biomarkers on proliferation, metastasis of HCC cells in vitro, and in vivo. The Kaplan-Meier (KM) plotter and ROC curves were used to validate the prognostic and diagnostic value of biomarker expression. Results: All the selected biomarkers were upregulated in HCC samples and higher expression levels were associated with advanced tumor stages and T grades. The regulation of YWHAB, PPAT, NOL10 promoter methylation varied in tumors, and precancerous normal tissues. Immune infiltration analysis suggested that the abnormal regulations of these biomarkers were likely attributed to B cells and dendritic cells. GSVA for these biomarkers showed their great contributions to proliferation of HCC. Specific Hu et al. Novel Biomarkers for Prognosis of Hepatocellular Carcinoma inhibition of their expression had strong effects on tumorigenesis in vitro and in vivo. ROC and KM curves confirmed their usefulness of diagnosis and prognosis of HCC. Conclusions: These findings identified YWHAB, PPAT, and NOL10 as novel biomarkers and validated their diagnostic and prognostic value for HCC.

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Section: Discussionmentioning

confidence: 99%

Identification and Validation of Novel Biomarkers for Diagnosis and Prognosis of Hepatocellular Carcinoma

Bao

Huang

et al. 2020

Front. Oncol.

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“…BRC1 was reported to be a potential prognostic biomarker in various tumors, such as adrenocortical carcinoma (Xu W. H. et al, 2019) and non-muscle invasive bladder cancer (Shi et al, 2019). IGF2BP3 is a prognostic marker of poor outcome for colorectal cancer , glioma (Gao Q. et al, 2019;Zhang et al, 2019), and papillary renal cell carcinoma . The overexpression of KIF2C has been significantly associated with poor prognosis of HCC (Chen et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Identification of Crucial Genes Associated With Immune Cell Infiltration in Hepatocellular Carcinoma by Weighted Gene Co-expression Network Analysis

Wang

Liu

et al. 2020

Front. Genet.

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“…To explore effective biomarkers for HCC diagnosis at early stage, multiple kinds of omics studies have been performed with samples from HCC patients or HCC cell lines, such as genomics, transcriptomics, proteomics, metabolomics, and so on. These omics studies provided huge number of molecules including circulating tumor DNA (ctDNA), circulating miRNAs, proteins, and metabolites as biomarker candidates for clinical HCC diagnosis (Tang et al, 2016;Zhou et al, 2011;Dittharot et al, 2018;Gao et al, 2019). Based on the data from omics studies, several effective biomarkers were identified and validated in clinical samples from HCC patients, among which AFP was the most widely used protein biomarker for early diagnosis of HCC (Marrero et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Lysine Acetylome Study of Human Hepatocellular Carcinoma Tissues for Biomarkers and Therapeutic Targets Discovery

Zhao

Zhang

et al. 2020

Front. Genet.

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Lysine acetylation is a vital post-translational modification (PTM) of proteins, which plays an important role in cancer development. In healthy human liver tissues, multiple non-histone proteins were identified with acetylation modification, however, the role of acetylated proteins in hepatocellular carcinoma (HCC) development remains largely unknown. Here we performed a quantitative acetylome study of tumor and normal liver tissues from HCC patients. Overall, 598 lysine acetylation sites in 325 proteins were quantified, and almost 59% of their acetylation levels were significantly changed. The differentially acetylated proteins mainly consisted of non-histone proteins located in mitochondria and cytoplasm, which accounted for 42% and 24%, respectively. Bioinformatics analysis showed that differentially acetylated proteins were enriched in metabolism, oxidative stress, and signal transduction processes. In tumor tissues, 278 lysine sites in 189 proteins showed decreased acetylation levels, which occupied 98% of differentially acetylated proteins. Moreover, we collected twenty pairs of tumor and normal liver tissues from HCC male patients, and found that expression levels of SIRT1 (p = 0.002), SIRT2 (p = 0.01), and SIRT4 (p = 0.045) were significantly up-regulated in tumor tissues. Over-expression of possibly accounted for the widespread deacetylation of non-histone proteins identified in HCC tumor tissues, which could serve as promising predictors of HCC. Taken together, our work illustrates abundant differentially acetylated proteins in HCC tumor tissues, and offered insights into the role of lysine acetylation in HCC development. It provided potential biomarker and drug target candidates for clinical HCC diagnosis and treatment.

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Integrated Proteogenomic Characterization of HBV-Related Hepatocellular Carcinoma

Cited by 668 publications

References 83 publications

Identification and Validation of Novel Biomarkers for Diagnosis and Prognosis of Hepatocellular Carcinoma

Identification and Validation of Novel Biomarkers for Diagnosis and Prognosis of Hepatocellular Carcinoma

Identification of Crucial Genes Associated With Immune Cell Infiltration in Hepatocellular Carcinoma by Weighted Gene Co-expression Network Analysis

Lysine Acetylome Study of Human Hepatocellular Carcinoma Tissues for Biomarkers and Therapeutic Targets Discovery

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