Molecular characterization of hepatocarcinogenesis using XXXX models.

@entity1 @entity66 @entity19 @entity5 @entity4078 @entity157 @entity99
UNASSIGNED: @entity157 ( @entity157 ) is a @entity66 , often unnoticed till the late stages, where treatment options become limited. Thus, there is a critical need to identify biomarkers for early detection of the developing @entity157 , as well as molecular pathways that would be amenable to therapeutic intervention. While analysis of @entity1 @entity157 tissues and serum components may serve these purposes, inability of early detection also precludes possibilities of identification of biomarkers or pathways that are sequentially perturbed at earlier phases of disease progression. We have therefore explored the option of utilizing @entity19 models to understand in a systematic and longitudinal manner the molecular pathways that are progressively deregulated by various etiological factors in contributing to @entity157 formation, and report the initial findings in characterizing their validity. Hepatitis B surface antigen @entity19 was used as a @entity99 model, which have been exposed to @entity4078 at various stages in life. Our findings confirm a synergistic effect of both these etiological factors, with a gender bias towards males for @entity157 predisposition. Time-based @entity4078 treatment also demonstrated the requirement of non-quiescent liver for effective transformation. @entity5 from these models with various etiologies resemble @entity1 HCCs histologically and at the molecular level. Extensive molecular characterization revealed the presence of a 11-gene @entity157 -expression signature that was able to discern transformed @entity1 hepatocytes from primary cells regardless of etiology, and from other @entity5 types. Moreover, distinct molecular pathways appear to be deregulated by various etiological agents en route to formation of HCCs, in which common pathways converge, highlighting the existence of etiology-specific as well as common @entity157 -specific molecular perturbations. This study therefore highlights the utility of these @entity19 models, which provide a rich resource for the longitudinal analysis of molecular changes and biomarkers associated with @entity157 that could be exploited further for therapeutic targeting.
