scholarly journals Gene expression analysis of biopsy samples reveals critical limitations of transcriptome-based molecular classifications of hepatocellular carcinoma

2016 ◽  
Vol 2 (2) ◽  
pp. 80-92 ◽  
Author(s):  
Zuzanna Makowska ◽  
Tujana Boldanova ◽  
David Adametz ◽  
Luca Quagliata ◽  
Julia E. Vogt ◽  
...  
2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15666-e15666 ◽  
Author(s):  
Giorgia Marisi ◽  
Mario Scartozzi ◽  
Luca Faloppi ◽  
Giuseppe Francesco Foschi ◽  
Gianfranco Lauletta ◽  
...  

e15666 Background: Angiopoietin-2 (Ang-2) is a crucial angiogenic factor. By binding to its receptor Tie2, Ang-2 cooperates with the VEGF pathway to maintain normal physiological functions. In the presence of VEGF, Ang-2 destabilizes blood vessels and promotes vascular sprouting. In cancers, Ang-2 is linked to not only angiogenesis but also invasive and metastatic phenotypes. Although sorafenib exerts no significant activity against Tie2, the predictive value of Ang-2 has been explored in 2 studies. Llovet et al conducted a large biomarker study based on SHARP study. The authors found that a high baseline plasma Ang-2 level was an independent factor for poorer OS but not for reduced sorafenib efficacy. Polymorphism analysis seems to have more advantages than protein or gene expression analysis. Gene expression analysis is performed on biological material collected at a specific time in the natural history of the disease. It is also subject to the influence of a number of laboratory biases. Conversely, polymorphism analysis can be performed at any time during the course of the disease, is not substantially influenced by laboratory biases and is less expensive. In our study we analysed the role of ANG-2 polymorphisms in relation to clinical outcome in patients with hepatocellular carcinoma treated with sorafenib. Methods: We analyzed 135 patients with hepatocellular carcinoma treated with sorafenib. Peripheral blood samples or FFPE tumor tissues were available for DNA extraction and genotyping analysis. Nine Ang-2 polymorphisms were analyzed by direct sequencing or Real Time PCR method. Results: With regard to Ang4 rs55633437 was observed that patients carrying the allele GG were associated with a better PFS and OS. The variants GG were associated with a median OS of 16.9 months vs 6.5 months of variants GT and TT (p = 0.016). The variants GT and TT were associated with a median PFS of 2.94 months vs 4.67 months of variants GG (p = 0.03). These data were confirmed by multivariate analysis Conclusions: Ang4 rs55633437 could represent prognostic markers in patients with advanced hepatocellular carcinoma treated with sorafenib.


2006 ◽  
Vol 13 (2) ◽  
pp. 241-249 ◽  
Author(s):  
Chia-Chu Tsai ◽  
Kai-Wen Huang ◽  
Hsiao-Fen Chen ◽  
Bo-Wen Zhan ◽  
Yen-Han Lai ◽  
...  

2012 ◽  
Vol 35 (3) ◽  
pp. 163-173 ◽  
Author(s):  
Maddalena Frau ◽  
Maria M. Simile ◽  
Maria L. Tomasi ◽  
Maria I. Demartis ◽  
Lucia Daino ◽  
...  

2020 ◽  
Vol 11 ◽  
Author(s):  
Qingquan Bai ◽  
Haoling Liu ◽  
Hongyu Guo ◽  
Han Lin ◽  
Xuan Song ◽  
...  

A further understanding of the molecular mechanism of hepatocellular carcinoma (HCC) is necessary to predict a patient’s prognosis and develop new targeted gene drugs. This study aims to identify essential genes related to HCC. We used the Weighted Gene Co-expression Network Analysis (WGCNA) and differential gene expression analysis to analyze the gene expression profile of GSE45114 in the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas database (TCGA). A total of 37 overlapping genes were extracted from four groups of results. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analyses were performed on the 37 overlapping genes. Then, we used the STRING database to map the protein interaction (PPI) network of 37 overlapping genes. Ten hub genes were screened according to the Maximal Clique Centrality (MCC) score using the Cytohubba plugin of Cytoscape (including FOS, EGR1, EPHA2, DUSP1, IGFBP3, SOCS2, ID1, DUSP6, MT1G, and MT1H). Most hub genes show a significant association with immune infiltration types and tumor stemness of microenvironment in HCC. According to Univariate Cox regression analysis and Kaplan-Meier survival estimation, SOCS2 was positively correlated with overall survival (OS), and IGFBP3 was negatively correlated with OS. Moreover, the expression of IGFBP3 increased with the increase of the clinical stage, while the expression of SOCS2 decreased with the increase of the clinical stage. In conclusion, our findings suggest that SOCS2 and IGFBP3 may play an essential role in the development of HCC and may serve as a potential biomarker for future diagnosis and treatment.


2010 ◽  
Vol 11 (4) ◽  
pp. 261-268 ◽  
Author(s):  
Thorsten Maass ◽  
Ioannis Sfakianakis ◽  
Frank Staib ◽  
Markus Krupp ◽  
Peter R. Galle ◽  
...  

Genomics ◽  
2010 ◽  
Vol 95 (4) ◽  
pp. 217-223 ◽  
Author(s):  
Yuji Hodo ◽  
Shin-ichi Hashimoto ◽  
Masao Honda ◽  
Taro Yamashita ◽  
Yutaka Suzuki ◽  
...  

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