@entity157 ( @entity157 ) is the fifth most common @entity5 worldwide and the third most common @entity5 in Asia. @entity157 has heterogeneous etiologic and molecular profiles and a varied response to therapeutics. The high recurrence rate and curtailed survival in this @entity5 are attributed to its resistance to therapy. The ultimate goal is to develop a more effective personalized therapeutic strategy for @entity157 , but the first step is to develop a system for classifying the disease on the basis of molecular biomarkers. To that end, we performed mRNA and microRNA (miRNA) expression profiling in 100 @entity157 tissues. Clustering analysis of informative genes identified two robust subtypes, which were validated by an independent dataset. The subtype characterized by a @entity5 stem cell-like signature was clinically aggressive and associated with poor survival. Integrated analysis of miRNA and mRNA expression in this subtype showed that @entity13823 was expressed at a significantly lower level in these @entity5 than in the other subtype. @entity13823 has been shown to directly suppress the expression of @entity15703 ( @entity15703 ), a key receptor in the signaling pathway of the bone morphogenetic proteins (BMPs), which regulate many stem cell markers as well as the clinically important cytokine @entity687 ( @entity687 ). Increased expression of @entity15703 and its downstream genes @entity5960 , @entity11707 , @entity5399 , and @entity687 was associated with shorter survival in a larger cohort of 227 @entity157 cases. Introduction of @entity13823 resulted in suppressed @entity5 phenotypes both in vitro and in vivo. CONCLUSION: We identified a clinically aggressive stem cell-like subtype of @entity157 that is characterized by an @entity13823 - @entity15703 - @entity6861 -Wnt circuit. We propose that @entity13823 may serve as a prognostic biomarker and therapeutic target for this subtype of @entity157 .

Regulatory @entity13823 - @entity15703 / XXXX circuit defines a @entity5 .

@entity5960 :: ('4072', 'Gene') :: ['EPCAM'] @entity15703 :: ('90', 'Gene') :: ['activin A receptor type 1', 'ACVR1'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer', 'malignancy', 'tumors'] @entity13823 :: ('406940', 'Gene') :: ['MiR-148a', 'miR-148a'] @entity11707 :: ('100133941', 'Gene') :: ['CD24'] @entity5399 :: ('7070', 'Gene') :: ['CD90'] @entity157 :: ('MESH:D006528', 'Disease') :: ['HCC', 'Hepatocellular carcinoma'] @entity687 :: ('3576', 'Gene') :: ['interleukin-8', 'IL-8'] @entity6861 :: ('649', 'Gene') :: ['BMP']
@entity6861 :: (649,Gene) :: ['BMP']
