Hepatocellular carcinoma(HCC)is a heterogeneous disease and the second most common cause of cancer-related death worldwide.Marked developments in genomic technologies helped scientists to understand the heterogeneity ...Hepatocellular carcinoma(HCC)is a heterogeneous disease and the second most common cause of cancer-related death worldwide.Marked developments in genomic technologies helped scientists to understand the heterogeneity of HCC and identified multiple HCC-related molecular subclasses.An integrative analysis of genomic datasets including 196 patients from The Cancer Genome Atlas(TCGA)group has recently reported a new HCC subclass,which contains three subgroups(iCluster1,iCluster2,and iCluster3).However,the transcriptional molecular characteristics underlying the iClusters have not been thoroughly investigated.Herein,we identified a more aggressive subset of HCC patients in the iCluster1,and re-clustered the TCGA samples into novel HCC subclasses referred to as aggressive(Ag),moderate-aggressive(M-Ag),and less-aggressive(L-Ag)subclasses.The Ag subclass had a greater predictive power than the TCGA iCluster1,and a higher level of alpha fetoprotein,microscopic vascular invasion,immune infiltration,isocitrate dehydrogenase 1/2 mutation status,and a worse survival than MAg and L-Ag subclasses.Global transcriptomic analysis showed that activation of hedgehog signaling in the Ag subclass may play key roles in tumor development of aggressive HCC.GLI1,a key transcriptional regulator of hedgehog signaling upregulated in the Ag subclass,was correlated with poor prognosis of HCC,and may be a potential prognostic biomarker and therapeutic target for Ag subclass HCC patients.展开更多
基金financial support from the National Key Program for Basic Research of China (2017YFC0906603, 2017YFC0908404, 2016YFA0501300)the National Natural Science Foundation of China (81530021)+1 种基金the Beijing Municipal Science and Technology Project (Z161100002616036)the Innovation Foundation of Medicine (BWS14J052, 16CXZ027)
文摘Hepatocellular carcinoma(HCC)is a heterogeneous disease and the second most common cause of cancer-related death worldwide.Marked developments in genomic technologies helped scientists to understand the heterogeneity of HCC and identified multiple HCC-related molecular subclasses.An integrative analysis of genomic datasets including 196 patients from The Cancer Genome Atlas(TCGA)group has recently reported a new HCC subclass,which contains three subgroups(iCluster1,iCluster2,and iCluster3).However,the transcriptional molecular characteristics underlying the iClusters have not been thoroughly investigated.Herein,we identified a more aggressive subset of HCC patients in the iCluster1,and re-clustered the TCGA samples into novel HCC subclasses referred to as aggressive(Ag),moderate-aggressive(M-Ag),and less-aggressive(L-Ag)subclasses.The Ag subclass had a greater predictive power than the TCGA iCluster1,and a higher level of alpha fetoprotein,microscopic vascular invasion,immune infiltration,isocitrate dehydrogenase 1/2 mutation status,and a worse survival than MAg and L-Ag subclasses.Global transcriptomic analysis showed that activation of hedgehog signaling in the Ag subclass may play key roles in tumor development of aggressive HCC.GLI1,a key transcriptional regulator of hedgehog signaling upregulated in the Ag subclass,was correlated with poor prognosis of HCC,and may be a potential prognostic biomarker and therapeutic target for Ag subclass HCC patients.
