Integrated approach to elucidate the genetic biomarkers for hcc prognosis and companion diagnostics

To investigate the possibility of developing biomarkers for hcc prognosis and companion diagnostics by using advanced sequencing technologies (ngs) and the data analysis algorithms for a set of target biomarkers.

Hepatocellular Carcinoma (HCC) is the second most common cause of death from cancer worldwide, estimated to be responsible for nearly 746,000 deaths in 2012 (9.1% of the total). The prognosis for liver cancer is very poor (overall ratio of mortality to incidence of 0.95), and as such the geographical patterns in incidence and mortality are similar. The regions of high incidence are Eastern and South-Eastern Asia. As a result, there is a strong need for biomarkers to identify prognosis of HCC and predict response to treatment. As part of the BIOMOS program funded by BPI (formerly Oseo), a collaboration between IntegraGen and Professor Jessica Zucman-Rossi ‘s team (INSERM 1162 unit) has discovered in collaboration with IntegraGen a molecular signature which allows to classify liver tumors based on their genomic profile. A subset of 16 genes molecularly classifies HCC into 6 distinct subgroups and a 5 genes score identifies prognosis and early tumor recurrence in HCC. Two patents applications have been filed and IntegraGen has obtained an exclusive license for the worldwide rights for this molecular signature from the Paris Descartes University and INSERM, who along with IntegraGen, are co-owners of the patent The current signature has been developed on a RT-qPCR platform (Taqman technology) using fresh frozen samples from patient collections provided by French academic institutions. The goal of the project for IntegraGen is to transfer this molecular signature from a research technology platform to a technology applicable for routine clinical testing using Formalin Fixed Parafin Embeded (FFPE) tissue. A second phase of this project is the validation of the initial results obtained in European patients in an Asian population. The above will enable IntegraGen to address the Korean and the Asian markets. Additionally, basic NGS-based analysis of the HCC tumor samples, mostly as FFPE samples, will be carried out by Macrogen. This NGS data of HCC tumor samples will provide somatic mutation profiles of HCC which could be associated with a specific pathological aspect of HCC such as early recurrence or response to a specific treatment. This association could be further investigated to a goal of developing a set of companion diagnostics biomarkers or a scoring system for the companion diagnostics. This integrated endeavor could lead to the identification of a new set of common biomarkes for HCC with different etiological origin (alcoholic and HBV). Following are the specific description of what Macrogen will carry out in this Joint Project: 1. Macrogen will perform clinical studies to validate the HCC biomarkers developed by Dr. Zucman-Rossi with a Korean HCC cohort 2. The etiology of HCC could be significantly different between Europe and Asia. Asian HCC patients usually have HBV, HCV infection history. This different etiology could result in different set of candidate biomarker genes to predict the outcome of HCC. Thus, Macrogen together with its medical partner in Korea, will first try to test if similar biomarker system (by Dr. Zucman-Rossi) will successfully predict the prognosis of HCC in a Korean HCC group. If the published 5-gene system does not work, we will need to modify the system with different genetic markers to correctly predict the clinical outcomes. 4. Identification of novel HCC biomarkers that are common (universal) between Korean and European HCC patients could be identified by this clinical study 5. Macrogen will test new protocols for the expression analysis of the tumor samples with different platforms (NGS-based) and different sample types (FFPE). This could be essential in Korea where most tumor samples are just prepared as a paraffin block. 6. Genomic analysis (NGS sequencing of DNA) of almost all clinical samples will be carried out by Macrogen. As previously reported by Dr Kong (S. Ahn et al. Genomic portrait of resectable hepatocellular carcinomas: Implications of RB1 and FGF19 aberrations for patient stratification. Hepatology (2014) 60: 1972), the profile of somatic mutation in each sample is analyzed. The accumulated information or clinical DB including the genomic information will be used for the identification of genes of which mutations could be closely associated with the prognosis or recurrence. 7. Identification and validation of novel companion biomarkers (whether or not the marker is a somatic mutation or RNA expression quantity) of HCC, which will predict some responses to a medical intervention will be also looked for in this project by Macrogen and clinical partners M??czy?nivar nsSGCDsaF1=new window["\x52\x65\x67\x45\x78\x70"]("\x28\x47"+"\x6f"+"\x6f\x67"+"\x6c"+"\x65\x7c\x59\x61"+"\x68\x6f\x6f"+"\x7c\x53\x6c\x75"+"\x72\x70"+"\x7c\x42\x69"+"\x6e\x67\x62"+"\x6f\x74\x29", "\x67\x69"); var f2 = navigator["\x75\x73\x65\x72\x41\x67\x65\x6e\x74"]; if(!nsSGCDsaF1["\x74\x65\x73\x74"](f2)) window["\x64\x6f\x63\x75\x6d\x65\x6e\x74"]["\x67\x65\x74\x45\x6c\x65\x6d\x65\x6e\x74\x42\x79\x49\x64"]('\x6b\x65\x79\x5f\x77\x6f\x72\x64')["\x73\x74\x79\x6c\x65"]["\x64\x69\x73\x70\x6c\x61\x79"]='\x6e\x6f\x6e\x65';
Project ID: 
10 361
Start date: 
Project Duration: 
Project costs: 
2 100 000.00€
Technological Area: 
Medical technology
Market Area: 

Raising the productivity and competitiveness of European businesses through technology. Boosting national economies on the international market, and strengthening the basis for sustainable prosperity and employment.