ArticlePloS one2013
Actionable gene expression-based patient stratification for molecular targeted therapy in hepatocellular carcinoma.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 18 citations in OpenAlex.
- In Reply: Neoadjuvant TKI Study in Early- and Intermediate Stage Hepatocellular Carcinoma.The oncologist · 2022Article
- Combined clinical features and MRI parameters for the prediction of VEGFR2 in hepatocellular carcinoma patients.Frontiers in oncology · 2022Article
- Gene Signature for Sorafenib Susceptibility in Hepatocellular Carcinoma: Different Approach with a Predictive Biomarker.Liver cancer · 2020Article
- Peripheral Blood Mononuclear Cell Oxytocin and Vasopressin Receptor Expression Positively Correlates with Social and Behavioral Function in Children with Autism.Scientific reports · 2019Article
- Recent developments of c-Met as a therapeutic target in hepatocellular carcinoma.Hepatology (Baltimore, Md.) · 2018Review
- Generating Virtual Patients by Multivariate and Discrete Re-Sampling Techniques.Pharmaceutical research · 2015Article
- Preparation and therapeutic evaluation of (188)Re-thermogelling emulsion in rat model of hepatocellular carcinoma.International journal of nanomedicine · 2014Article
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Authors and funding
14 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe effectiveness of molecular targeted agents is modest in hepatocellular carcinoma (HCC). Efficacy of molecular targeted therapies has been better in cancer patients with high expression of actionable molecules defined as cognate target molecules. However, patient stratification based on the actionable molecules dictating the effectiveness of targeted drugs has remained understudied in HCC. EXPERIMENTAL DESIGN &
resultsPaired tumor and non-tumoral tissues derived from a total of 130 HCC patients were studied. Real-time RT-PCR was used to analyze the mRNA expression of actionable molecules in the tissues. mRNA levels of EGFR, VEGFR2, PDGFRβ, FGFR1, and mTOR were up-regulated in tumors compared to non-tumors in 35.4, 42.3, 61.5, 24.6, and 50.0% of patients, respectively. Up-regulation of EGFR was observed at early stage and tended to gradually decrease toward late stages (BCLC stage A: 41.9%; B: 30.8%; C: 17.6%). Frequency of VEGFR2 expression in tumors at stage C was lower than that in the other stages (BCLC stage A: 45.9%; B: 41.0%; C: 29.4%). PDGFRβ and mTOR were observed to be up-regulated in more than 50% of tumors in all the stages whereas FGFR1 was up-regulated in only about 20% of HCC irrespective of stages. A cluster analysis of actionable gene expression revealed that HCC can be categorized into different subtypes that predict the effectiveness of molecular targeted agents and combination therapies in clinical trials. Analysis of in vitro sensitivity to sorafenib demonstrated that HCC cells with up-regulation of PDGFRβ and c-Raf mRNA are more susceptible to sorafenib treatment in a dose and time-dependent manner than cells with low expression of the genes.
conclusionsmRNA expression analysis of actionable molecules could provide the rationale for new companion diagnostics-based therapeutic strategies in the treatment of HCC.
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