Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multifocal Hepatocellular carcinoma (HCC) may be multiple HCCs of multicentric origin (MO) or intrahepatic metastases (IM) arising from a primary HCC. Numerous attempts to differentiate the two types of multifocal HCC have been made including the valuation of the clinicopathologic characteristics of MO and IM patients and the recurrence time, loss-of-heterozygosity analysis of specific DNA microsatellite loci to distinguish multiclonal MO from IM of monoclonal origin, and the research of diagnostic and progression markers through genomic and proteomic analyses. These approaches, however, have been unsatisfactory hitherto. Recently, a multi-omic analysis of HBV-related multifocal HCCs, including intergraded genomics and transcriptomics, was performed and the results, validated by a cohort of 174 HCC patients, were correlated with HCC clinicopathological data. The two multifocal HCC types were effectively discerned by multi-omics profiling that could predict HCC clonality and aggressiveness. Further, the dual-specificity protein kinase TTK was recognized as a prognostic marker for HCC. Multi-omics strategy potentially opens new perspectives for the diagnosis, prognosis and personalized treatment of multi-focal HCC. Further work aimed at extending this strategy to HCC with other etiology, simplifying the analysis, and reducing its costs is necessary for its routine clinical application.
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PMID:Multifocal hepatocellular carcinoma: intrahepatic metastasis or multicentric carcinogenesis? 2570 36

Therapies for primary liver cancer, the third leading cause of cancer-related death worldwide, remain limited. Following multi-omics analysis (including whole genome and transcriptome sequencing), we were able to identify the dual-specific protein kinase TTK as a putative new prognostic biomarker for liver cancer. Herein, we show that levels of TTK protein are significantly elevated in neoplastic tissues from a cohort of liver cancer patients, when compared with adjacent hepatic tissues. We also tested the utility of TTK targeted inhibition and have demonstrated therapeutic potential in an experimental model of liver cancer in vivo. Following lentiviral shRNA knockdown in several human liver cancer cell lines, we demonstrated that TTK boosts cell growth and promotes cell spreading; as well as protects against senescence and decreases autophagy. In an experimental animal model, we show that in vitro knockdown of TTK effectively blocks intrahepatic growth of human HCC xenografts. Furthermore, we note that, in vivo silencing of TTK, by systemically delivering TTK siRNAs to already tumor-bearing liver, limits intrahepatic spread of liver cancer cells. This intervention is associated with decreased tumor aggressiveness, as well as increased senescence and autophagy. Taken together, our data suggest that targeted TTK inhibition might have clinical utility as an adjunct therapy in management of liver cancer.
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PMID:Utility of the dual-specificity protein kinase TTK as a therapeutic target for intrahepatic spread of liver cancer. 2761 77