Abstract: Adeno-associated virus (AAV) is a defective mono-stranded DNA virus, endemic in human population (35-80%). Recurrent clonal AAV2 insertions are associated with the pathogenesis of rare human hepatocellular carcinoma (HCC) developed on normal liver. The aimed of the inventors was to characterize the natural history of AAV infection in the liver. Viral DNA was thus quantified in tumor and non-tumor liver tissues of 1461 patients. Presence of episomal form and viral mRNA expression were analyzed using a DNAse/TaqMan based assay and quantitative RT-PCR. In silico analyses using viral capture data explored viral variants and new clonal insertions. AAV DNA was detected in 21% of the patients equally distributed in 2 major viral subtypes: one similar to AAV2, the other hybrid between AAV2 and AAV13 sequences. Thus the inventors provided an integrated analysis of the wild type AAV infection in the liver with the identification of viral genotypes, molecular forms, helper virus relationship and viral integrations.

Abstract: The present invention relates to the technical field of liver diseases, their classification and diagnosis. It provides a new method for classifying a liver sample between non-hepatocellular sample; hepatocellular carcinoma (HCC) sample with further classification into one of subgroups G1 to G6; focal nodule dysplasia (FNH) sample; hepatocellular adenoma (HCA) sample with further classification into HNF1A mutated HCA, inflammatory HCA, ? catenin mutated HCA or other HCA sample; and other benign liver sample, based on determination in vitro of genes expression profiles and analysis of the expression profile using algorithms calibrated with reference samples. The invention also provides kits for the classification of liver samples, and methods of treatment of liver disease in a subject based on a preliminary classification of a liver sample of said subject.

Abstract: The present invention relates to the technical field of hepatocellular carcinoma (HCC) management, and more precisely to the prognosis of HCC aggressiveness and associated therapeutic decisions. The invention provides a new prognosis method of HCC aggressiveness, based on determination in vitro and analysis of an expression profile comprising genes TAF9, RAMP3, HN1, KRT19, and RAN. The invention also provides kits for the prognosis of HCC aggressiveness, and methods of treatment of HCC in a subject based on a preliminary prognosis of said subject HCC aggressiveness.

Abstract: Methodology for the in vitro classification and/or prognosis of hepatocellular carcinoma (HCC) from a HCC sample is based on the determination of the expression profile of particular gene combinations. For example, in one embodiment, a method comprises measuring the expression level in an HCC sample of at least 8 genes selected from the group consisting of: RAB1A, REG3A, NRAS, RAMP3, MERTK, PIR, EPHA1, LAMA3, G0S2, HN1, PAK2, AFP, CYP2C9, CDH2, HAMP, SAE1, ADH6, DCN, FLJ10159, ALDH1L1, IGF1, LECT2, SLC38A1, SPARCL1, CTNNA2, GLUL, LEF1, MATN2, MME, PFN2, SPINT2, TBX3, and FGFR2; b) calculating 6 subgroup distances from the expression profile; and c) classifying the HCC tumor in the subgroup for which the subgroup distance is the lowest, wherein the 6 subgroups G1, G2, G3, G4, G5, and G6 are defined by the presence (+) or absence (?) of their clinical and genetic features.

Abstract: Methodology for the in vitro classification and/or prognosis of hepatocellular carcinoma (HCC) from a HCC sample is based on the determination of the expression profile of particular gene combinations. For example, in one embodiment, a method comprises measuring the expression level in an HCC sample of at least 8 genes selected from the group consisting of: RAB1A, REG3A, NRAS, RAMP3, MERTK, PIR, EPHA1, LAMA3, G0S2, HN1, PAK2, AFP, CYP2C9, CDH2, HAMP, SAE1, ADH6, DCN, FLJ10159, ALDH1L1, IGF1, LECT2, SLC38A1, SPARCL1, CTNNA2, GLUL, LEF1, MATN2, MME, PFN2, SPINT2, TBX3, and FGFR2; b) calculating 6 subgroup distances from the expression profile; and c) classifying the HCC tumor in the subgroup for which the subgroup distance is the lowest, wherein the 6 subgroups G1, G2, G3, G4, G5, and G6 are defined by the presence (+) or absence (?) of their clinical and genetic features.

Abstract: Methodology for the in vitro classification and/or prognosis of hepatocellular carcinoma (HCC) from a HCC sample is based on the determination of the expression profile of particular gene combinations.