| Even to this day,liver cancer still ranks top the list of mortality among all cancers.In our country and in southeastern Asia area,the morbidity of Hepatocellular carcinoma(HCC)is very high,and it is the major type of liver cancer.Because lack of effective diagnostic biomarker,HCC patients are already in progressive stage or late stage when diagnosed,thus there is very limited treatment available,generally resulting in poor prognosis,short overall survival and high mortality.Although,at the present,AFP,AFP-L3 are main diagnosis biomarker clinically.However,due to the heterogen eity of HCC,these biomarkers are not ideal in term of senisitivity and specficity.Therefore,it’s urgently needed to find more effective biomarkers for HCC early detection.Based on our preliminary work,we found that PPP1CA level in blood is significantly higher in HCC patients compared to in control who were diagnosed with other liver disease or healthy.In our current project,we screened samples of patients with different liver disease or in different stages of HCC,according to its progression and etiology.ELISA method is used to detect PPP1CA level and we use non-parameters tests,Spearman correlation test and ROC curve to investigate possible application and value of PPP1CA in clinics.And we found for the first time that PPP1C A is significantly higher in BCLC B-D stages than in BCLC A stage,and is correlated with HBV-induced HCC.PPP1CA has higher sensitivity than AFP.The combination of PPP1CA and AFP can improve the sensitivity of diagnostic test and has better consistency with gold standard.Next,according to the correlation between PPP1CA and tumor size,we construct some plasmids and virus for overexpression or knock-down of PPP 1C A,and try to find out the role of PPP 1 CA in HCC proliferation.We found that overexpression of PPP1C A in HCC cell lines promotes cell proliferation while knock-down of PPP1CA inhibits cell proliferation,and this phenomenon may be related with dephosphorylation of YAP,a co-acti viator of Hippo pathway.At last,based on the potential clinical use and the advantages of chemilumineseent immunoassay(CLIA)which are lower noise and lower detection limit,we are trying to establish the CLIA method for detecting PPP1CA level in blood samples,some initial and basic work are done in this thesis. |
