Identification of circulating protein biomarkers in patients with hepatocellular carcinoma concomitantly infected with chronic hepatitis C virus

Wahab, Abdel; El-Halawany, Medhat S.; Emam, Ahmed A.; Elfiky, Ammar; Elmageed, Zakaria Y. Abd

doi:10.1080/1354750x.2016.1252966

Cited by 10 publications

(8 citation statements)

References 42 publications

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“…Biomarkers with gender disparity for HCC and oncogene expression have not been well established. SAA2 and ORM2 had been reported to be significantly up-regulated in HCC patients and been suggested as potential biomarkers [45][46][47]. For SERPINA1, the polymorphisms, fucosylation, and up-regulation of its isoforms have been suggested to be related to hepatocarcinogenesis, metastasis, and sorafenib-resistant [48][49][50].…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis revealed common, unique and systemic signatures in gender-dependent hepatocarcinogenesis

Rong

Wang

et al. 2020

Biol Sex Differ

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Hepatocellular carcinoma (HCC) is the most common liver cancer and is highly malignant. Male prevalence and frequent activation of the Ras signaling pathway are distinct characteristics of HCC. However, the underlying mechanisms remain to be elucidated. By exploring Hras12V transgenic mice showing male-biased hepatocarcinogenesis, we performed a high-throughput comparative proteomic analysis based on tandem-masstag (TMT) labeling combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) on the tissue samples obtained from HCC (T) and their paired adjacent precancerous (P) of Hras12V transgenic male and female mice (Ras-Tg) and normal liver (W) of wild-type male and female mice (Non-Tg). The further validation and investigation were performed using quantitative real-time PCR and western blot. Totally, 5193 proteins were quantified, originating from 5733 identified proteins. Finally, 1344 differentially expressed proteins (DEPs) (quantified in all examined samples; |ratios| ≥ 1.5, p < 0.05) were selected for further analysis. Comparison within W, P, and T of males and females indicated that the number of DEPs in males was much higher than that in females. Bioinformatics analyses showed the common and unique cluster-enriched items between sexes, indicating the common and gender-disparate pathways towards HCC. Expression change pattern analysis revealed HCC positive/ negative-correlated and ras oncogene positive/negative-correlated DEPs and pathways. In addition, it showed that the ras oncogene gradually and significantly reduced the responses to sex hormones from hepatocytes to hepatoma cells and therefore shrunk the gender disparity between males and females, which may contribute to the cause of the loss of HCC clinical responses to the therapeutic approaches targeting sex hormone pathways. Additionally, gender disparity in the expression levels of key enzymes involved in retinol metabolism and terpenoid backbone/steroid biosynthesis pathways may contribute to male prevalence in hepatocarcinogenesis. Further, the biomarkers, SAA2, Orm2, and Serpina1e, may be sex differences. In conclusion, common and unique DEPs and pathways toward HCC initiated by ras oncogene from sexually dimorphic hepatocytes provide valuable and novel insights into clinical investigation and practice.

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Section: Discussionmentioning

confidence: 99%

Proteomic analysis revealed common, unique and systemic signatures in gender-dependent hepatocarcinogenesis

Rong

Wang

et al. 2020

Biol Sex Differ

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“…It participates in blood coagulation, inflammatory response, apoptosis regulation and the prevention process of metastasis in cancer cells (38,39). KNG1 is overexpressed in CRC and HCC (40) and is regarded as a potential prognostic marker for CRC, as patients with increased KNG1 expression exhibit decreased survival rates when compared with lower KNG1 expression patients (39,41). Additional studies reported that KNG1 may be involved in cholesterol and lipoprotein metabolism disturbance and take part in the complex interplay between the hemostatic system and immune response in hepatitis C virus (HCV)-associated HCC (39,40).…”

Section: Discussionmentioning

confidence: 99%

“…KNG1 is overexpressed in CRC and HCC (40) and is regarded as a potential prognostic marker for CRC, as patients with increased KNG1 expression exhibit decreased survival rates when compared with lower KNG1 expression patients (39,41). Additional studies reported that KNG1 may be involved in cholesterol and lipoprotein metabolism disturbance and take part in the complex interplay between the hemostatic system and immune response in hepatitis C virus (HCV)-associated HCC (39,40). Differences in KNG1 expression were observed among patients with multidrug-resistant and drug-sensitive tuberculosis and healthy control patients, and it is suspected that blood coagulation serves a role in the resistant ability of KNG1 (42).…”

Section: Discussionmentioning

confidence: 99%

Identification of key pathways and biomarkers in sorafenib‑resistant hepatocellular carcinoma using bioinformatics analysis

Huang

Yuan

et al. 2018

Exp Ther Med

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Hepatocellular carcinoma (HCC) is one of the most common malignant types of cancer, with a high mortality rate. Sorafenib is the sole approved oral clinical therapy against advanced HCC. However, individual patients exhibit varying responses to sorafenib and the development of sorafenib resistance has been a new challenge for its clinical efficacy. The current study identified gene biomarkers and key pathways in sorafenib-resistant HCC using bioinformatics analysis. Gene dataset GSE73571 was obtained from the Gene Expression Omnibus (GEO) database, including four sorafenib-acquired resistant and three sorafenib-sensitive HCC phenotypes. Differentially expressed genes (DEGs) were identified using the web tool GEO2R. Functional and pathway enrichment of DEGs were analyzed using the Database for Annotation, Visualization and Integrated Discovery and the protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape. A total of 1,319 DEGs were selected, which included 593 upregulated and 726 downregulated genes. Functional and pathway enrichment analysis revealed DEGs enriched in negative regulation of endopeptidase activity, cholesterol homeostasis, DNA replication and repair, coagulation cascades, insulin resistance, RNA transport, cell cycle and others. Eight hub genes, including kininogen 1, vascular cell adhesion molecule 1, apolipoprotein C3, alpha 2-HS glycoprotein, erb-b2 receptor tyrosine kinase 2, secreted protein acidic and cysteine rich, vitronectin and vimentin were identified from the PPI network. In conclusion, the present study identified DEGs and key genes in sorafenib-resistant HCC, which further the knowledge of potential mechanisms in the development of sorafenib resistance and may provide potential targets for early diagnosis and new treatments for sorafenib-resistant HCC.

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“…Noninvasive methods, including blood tests, are still very important. Published research has shown that PON1 is an enzyme that is mainly synthesized in the liver and released into the circulatory system [ 45 , 46 ]. The expression of PON1 is mainly affected by liver cells, and the use of PON1 in a predictive model may reduce other possible interference factors.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the prognostic value of paraoxonase 1 in the recurrence and metastasis of hepatocellular carcinoma and establishment of a liver-specific predictive model of survival

Fan

et al. 2018

J Transl Med

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BackgroundHepatocellular carcinoma is a malignant tumor with a highly invasive and metastatic phenotype, and the detection of potential indicators associated with its recurrence and metastasis after surgical resection is critical for patient survival.MethodsTranscriptome data for large cohorts (n = 1432) from multicenter sources were comprehensively analyzed to explore such potential signatures. The prognostic value of the selected indicators was investigated and discussed, and a comparison with conventional clinicopathological features was performed. A survival predictive nomogram for 5-year survival was established with the selected indicator using the Cox proportional hazards regression. To validate the indicator at the protein level, we performed immunohistochemical staining with paraffin-embedded slides of hepatocellular carcinoma samples (n = 67 patients) from our hospital. Finally, a gene set enrichment analysis (GSEA) was performed to detect the underlying biological processes and internal mechanisms.ResultsThe liver-specific protein paraoxonase 1 (PON1) was found to be the most relevant indicator of tumor recurrence, invasiveness, and metastasis in the present study, and the downregulation of PON1 might reveal poor survival for patients with hepatocellular carcinoma. The C-index of the PON1-related nomogram was 0.714, thus indicating a more effective predictive performance than the 7th American Joint Committee on Cancer (AJCC) tumor stage (0.534), AJCC T stage (0.565), or alpha-fetoprotein (0.488). The GSEA revealed that PON1 was associated with several hepatocellular carcinoma-related pathways, including the cell cycle, DNA replication, gap junction and p53 downstream pathways.ConclusionsThe downregulation of paraoxonase 1 may suggest worse outcomes and a higher recurrence rate. Thus, paraoxonase 1 might represent an indicator for predicting the survival of patients with hepatocellular carcinoma.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1707-0) contains supplementary material, which is available to authorized users.

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Identification of circulating protein biomarkers in patients with hepatocellular carcinoma concomitantly infected with chronic hepatitis C virus

Abstract: In HCC patients with chronic HCV infection, we identified a group of differentially expressed circulating proteins involved in regulating different cellular mechanisms.

Cited by 10 publications

References 42 publications

Proteomic analysis revealed common, unique and systemic signatures in gender-dependent hepatocarcinogenesis

Proteomic analysis revealed common, unique and systemic signatures in gender-dependent hepatocarcinogenesis

Identification of key pathways and biomarkers in sorafenib‑resistant hepatocellular carcinoma using bioinformatics analysis

Evaluation of the prognostic value of paraoxonase 1 in the recurrence and metastasis of hepatocellular carcinoma and establishment of a liver-specific predictive model of survival

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