Emerging signals regulating liver tumor initiating cells

Tumor initiating cells(TICs)have been identified as cells that account for tumor heterogeneity.Recent studies demonstrated that genes controlling stem cell biology play key roles in maintaining TICs and promote their development into cancer.In this review,we summarize findings from human and animal studies that indicate the presence of TICs during liver cancer development.Markers identified for liver development and regeneration are used to identify liver cancer TICs.Expression of these markers is often upregulated in human hepatocellular carcinoma(HCC)specimen.Using flow cytometry analysis and lineage tracing approaches,the presence of TICs is confirmed.Expression of TIC markers and the presence of TICs are also observed in genetically modified animals that target genes that are frequently altered in human HCC.The presence of these TICs represents a major challenge for therapeutic development.Elucidating signals that can regulate the fate,transformation and growth of liver TICs is an emerging need in liver research.Sex-determining region Y-box 9(SOX9)has recently become an important marker for liver TICs.Here,we summarize the role of SOX9 in TICs and its potential interaction with other signals.This includes the Notch-Numb signal that controls asymmetrical-symmetrical cell division,Wnt-b-catenin signal that maintains cell fate and transforming growth factor(TGF)-b signal that acts as upstream inducers.

Calcium channel α2δ1 subunit as a novel biomarker for diagnosis of hepatocellular carcinoma

Objective:Hepatocellular carcinoma(HCC)is the fifth most common malignancy worldwide.The identification of new simple,inexpensive and highly accurate markers for HCC diagnosis and screening is needed.This case-control study evaluates the role of annexin A2 and voltage-gated calcium channelsα2δ1 subunit as serum biomarkers for HCC diagnosis.Methods:The study comprised three groups:group 1,50 patients with an initial diagnosis of HCC associated with chronic hepatitis C virus infection;group 2,25 patients diagnosed with chronic hepatitis C virus infection and cirrhosis without any evidence of HCC;and group 3,15 healthy controls.All participants were subjected to clinical and laboratory investigations,and radiological scanning.The serum levels of alpha-fetoprotein(AFP),annexin A2,and theα2δ1 subunit were evaluated by using ELISA technique.Results:The serum levels of annexin A2 significantly increased in patients with HCC(10.4±2.5 ng/m L;P<0.001)or with cirrhosis(9.31±1.8 ng/m L;P<0.001)comparing to that of healthy controls(0.296±0.09 ng/m L).However,there was no significant difference in serum annexin A2 levels in patients with HCC comparing to those with cirrhosis.Serumα2δ1 subunit significantly increased in patients with HCC(20.12±3.7 ng/m L)comparing to that in patients with cirrhosis(10.41±3.4 ng/m L,P<0.001)and healthy controls(10.2±2.9 ng/m L,P<0.001).Conclusions:The serumα2δ1 subunit may function as a new biomarker for HCC diagnosis.Conversely,serum annexin A2 has low diagnostic value as an HCC marker,especially in patients with underlying cirrhosis.