Recognition of HER2 expression in hepatocellular carcinoma and its significance in postoperative tumor recurrence

Shi, Jihua; Guo, Wenzhi; Jin, Yang; Zhang, Huapeng; Pang, Chun; Li, Jie; Line, Pål–Dag; Zhang, Shuijun

doi:10.1002/cam4.2006

Cited by 45 publications

(50 citation statements)

References 29 publications

(44 reference statements)

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“…However, it is widely perceived that a drug choice based on biomarker analysis could improve the treatment outcome. Key RTK signaling/angiogenesis genes MET, ERBB2, KDR and EGFR, all implicated in HCC [49][50][51][52], negatively correlate with SOCS1, and the first two with SOCS3 as well. Deregulated EGFR and KDR signaling can contribute to Sorafenib resistance in advanced HCC [51,53].…”

Section: Discussionmentioning

confidence: 98%

Prognostic significance of SOCS1 and SOCS3 tumor suppressors and oncogenic signaling pathway genes in hepatocellular carcinoma

et al. 2020

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Background: SOCS1 and SOCS3 genes are considered tumor suppressors in hepatocellular carcinoma (HCC) due to frequent epigenetic repression. Consistent with this notion, mice lacking SOCS1 or SOCS3 show increased susceptibility to diethylnitrosamine (DEN)-induced HCC. As SOCS1 and SOCS3 are important regulators of cytokine and growth factor signaling, their loss could activate oncogenic signaling pathways. Therefore, we examined the correlation between SOCS1/SOCS3 and key oncogenic signaling pathway genes as well as their prognostic significance in HCC. Methods: The Cancer Genome Atlas dataset on HCC comprising clinical and transcriptomic data was retrieved from the cBioportal platform. The correlation between the expression of SOCS1 or SOCS3 and oncogenic pathway genes was evaluated using the GraphPad PRISM software. The inversely correlated genes were assessed for their impact on patient survival using the UALCAN platform and their expression quantified in the regenerating livers and DEN-induced HCC tissues of mice lacking Socs1 or Socs3. Finally, the Cox proportional hazards model was used to evaluate the predictive potential of SOCS1 and SOCS3 when combined with the genes of select oncogenic signaling pathways.

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Section: Discussionmentioning

confidence: 98%

Prognostic significance of SOCS1 and SOCS3 tumor suppressors and oncogenic signaling pathway genes in hepatocellular carcinoma

et al. 2020

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“…ERBB2 (also known as HER2) is closely linked to many enzymes, e.g. fatty acid synthase, which play essential regulatory roles in lipid metabolism or lipogenic pathways [75] and its hepatic expression has been identified in liver diseases [76, 77]. Remarkably, the hepatic gene expression of SDCBP has been found differentially expressed in steatotic liver [78].…”

Section: Discussionmentioning

confidence: 99%

Construction and Analysis of Protein-Protein Interaction Network of Non-Alcoholic Fatty Liver Disease

Amanatidou

Dedoussis

2020

Preprint

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Non-alcoholic fatty liver disease (NAFLD) is a disease with multidimensional complexities. Many attempts have been made over the years to treat this disease but its incidence is rising. For this reason, the need to identify and study new candidate NAFLD biomarkers is of utmost importance. Systems-based approaches such as the analysis of protein-protein interaction (PPI) network could lead to the discovery of new disease biomarkers that can then be translated into clinical practice. The aim of this study is to analyze the interaction network of human proteins associated with NAFLD as well as their experimentally verified interactors and to propose new candidate proteins that may be involved in this disease. Computational analysis made it feasible to detect 77 candidate proteins associated with NAFLD, having high network scores. Furthemore, clustering analysis was performed to identify densely connected regions with biological significance in this network. Additionally, gene expression analysis was conducted to validate part of the findings of this research work. We believe that our research will be helpful in extending experimental efforts to address the pathogenesis and progression of NAFLD.

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“…However, it is widely perceived that drug choice based on biomarker analysis could improve the treatment outcome. Key RTK signaling/angiogenesis genes MET, ERBB2, KDR and EGFR, all implicated in HCC [36,[70][71][72][73], negatively correlate with SOCS1, and the first two with SOCS3 as well. Deregulated EGFR and KDR signaling can contribute to Sorafenib resistance in advanced HCC [72,74].…”

Section: Rtk Signaling and Angiogenesis Pathwaysmentioning

confidence: 99%

Prognostic significance ofSOCS1andSOCS3tumor suppressors in hepatocellular carcinoma and its correlation to key oncogenic signaling pathways

Khan

Ghosh

Variya

et al. 2020

Preprint

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Suppressor of cytokine signaling (SOCS) proteins SOCS1 and SOCS3 are considered tumor suppressors in liver hepatocellular carcinoma (LIHC). To gain insight into the underlying molecular mechanisms, the expression of SOCS1/ SOCS3 was evaluated in The Cancer Genome Atlas LIHC dataset along with key oncogenic signaling pathway genes. SOCS1 expression was not significantly reduced in HCC yet higher expression predicted favorable prognosis, whereas SOCS3 lacked predictive potential despite lower expression. Only a small proportion of the cell cycle, receptor tyrosine kinase, growth factor and RAS-RAF-MEK-MAPK signaling genes negatively correlated with SOCS1 or SOCS3, of which even fewer showed elevated expression in HCC and predicted survival. However, many PI3K-AKT-MTOR pathway genes showed mutual exclusivity with SOCS1/SOCS3 and displayed independent predictive ability. Among genes that negatively correlated with SOCS1/SOCS3, CDK2, MLST8, AURKA, MAP3K4 and RPTOR showed corresponding modulations in the livers of mice lacking Socs1 or Socs3 during liver regeneration and in experimental HCC, and in Hepa1-6 murine HCC cells overexpressing SOCS1/SOCS3. However, Cox proportional hazards model identified CXCL8, DAB2 and PIK3R1 as highly predictive in combination with SOCS1 or SOCS3. These data suggest that developing prognostic biomarkers and precision treatment strategies based on SOCS1/SOCS3 expression need careful testing in different patient cohorts.Prognostic significance of SOCS1 and SOCS3 in HCC Khan et al.,3 genes that regulate hepatocyte proliferation and survival. Our findings show that the expression of SOCS1 and SOCS3 negatively correlates with several genes in a similar fashion, but also show distinct regulation of a number of genes in several oncogenic signaling pathways. The latter could explain, at least partly, the inability of SOCS3 to compensate for the loss of SOCS1 and vice versa in animal models of HCC. We identify SOCS1 but not SOCS3 as an independent prognostic factor, whereas both display improved predictive potential when combined with certain key genes of the oncogenic signaling pathways. Besides, our findings reveal important differences between published works on putative HCC biomarkers and the TCGA data, highlighting the need for further studies on prognostic biomarkers for precision HCC therapy.

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Recognition of HER2 expression in hepatocellular carcinoma and its significance in postoperative tumor recurrence

Cited by 45 publications

References 29 publications

Prognostic significance of SOCS1 and SOCS3 tumor suppressors and oncogenic signaling pathway genes in hepatocellular carcinoma

Prognostic significance of SOCS1 and SOCS3 tumor suppressors and oncogenic signaling pathway genes in hepatocellular carcinoma

Construction and Analysis of Protein-Protein Interaction Network of Non-Alcoholic Fatty Liver Disease

Prognostic significance ofSOCS1andSOCS3tumor suppressors in hepatocellular carcinoma and its correlation to key oncogenic signaling pathways

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