Background:Glioma,the most frequent primary tumor of the central nervous system,has poor prognosis.The epidermal growth factor receptor(EGFR)pathway and angiogenesis play important roles in glioma growth,invasion,and ...Background:Glioma,the most frequent primary tumor of the central nervous system,has poor prognosis.The epidermal growth factor receptor(EGFR)pathway and angiogenesis play important roles in glioma growth,invasion,and recurrence.The present study aimed to use proteomic methods to probe into the role of the EGF-EGFR-angiogenesis axis in the tumorigenesis of glioma and access the therapeutic efficacy of selumetinib on glioma.Methods:Proteomic profiling was used to characterize 200 paired EGFRpositive and EGFR-negative glioma tissues of all pathological types.The quantitative mass spectrometry data were used for systematic analysis of the proteomic profiles of 10 EGFR-positive and 10 EGFR-negative glioma cases.Consensusclustering analysis was used to screen target proteins.Immunofluorescence analysis,cell growth assay,and intracranial xenograft experiments were used to verify and test the therapeutic effect of selumetinib on glioma.Results:Advanced proteomic screening demonstrated that the expression of EGF-like domain multiple 7(EGFL7)was higher in EGFR-positive tumor tissues than in EGFR-negative tumor tissues.In addition,EGFL7 could act as an activatorin vitro and in vivo to promote glioma cell proliferation.EGFL7 was associated strongly with EGFR and prognosis.EGFL7 knockdown effectively suppressed glioma cell proliferation.Selumetinib treatment showed tumor reduction effect in EGFR-positive glioblastoma xenograft mouse model.Conclusions:EGFL7 is a potential diagnostic biomarker and therapeutic target of glioma.Selumetinib could target the EGFR pathway and possibly improve the prognosis of EGFR-positive glioma.展开更多
Objective: To detect the expression and location of TGF-β1, ADAM12 and HB-EGF in primary hepatic carcinoma and study their effect on the growth and metastasis of hepatoma carcinoma cell. Methods: TGF-β1, ADAM12 and ...Objective: To detect the expression and location of TGF-β1, ADAM12 and HB-EGF in primary hepatic carcinoma and study their effect on the growth and metastasis of hepatoma carcinoma cell. Methods: TGF-β1, ADAM12 and HB-EGF were detected by RT-PCR and immunohistochemistry in 30 cases of hepatic carcinoma tissues, 30 cases of adjacent carci- noma tissues and 5 cases of normal hepatic tissues. Results: RT-PCR analyses showed that the mRNA expression of TGF-β1, ADAM12 and HB-EGF were markedly increased in each hepatic carcinoma tissue compared with its adjacent tissue (P < 0.01), but no signal was detected in normal hepatic tissue. Immunohistochemistry showed the same outcome on the expression of above three factors in hepatic tissues as RT-PCR. Proteins location analyses showed the proteins of TGF-β1, ADAM12 and HB-EGF all distributed in the stroma of hepatic carcinoma tissues. The positive correlation was found between TGF-β1 and ADAM12 (r = 0.6137, P < 0.05), as well as ADAM12 and HB-EGF (r = 0.5763, P < 0.05). The protein expression of TGF-β1, ADAM12 and HB-EGF were correlated with the size of tumors, degree of differentiation of hepatoma carcinoma cells, portal vein thrombus and the metastasis of absorbent glands, especially with hepatic cirrhosis caused by hepatitis B virus. Conclu- sion: TGF-β1, ADAM12 and HB-EGF possibly play an important role in the process of growth, invasion and metastasis of hepatoma carcinoma cell, meanwhile, the above three factors may collectively participate in the transition from hepatic cirrhosis caused by hepatitis B virus to hepatocellular carcinoma.展开更多
基金This work was supported by grants from the National Natural Science Foundation of China(81770781 to XJL)Hunan Provincial Innovation Foundation for Postgraduate(CX2018B114 to FYFW)+1 种基金the Fundamental Research Funds for the Central Universities of Central South University(2018zzts043 to FYFW)China Scholarship Council(201806370130 to FYFW).
文摘Background:Glioma,the most frequent primary tumor of the central nervous system,has poor prognosis.The epidermal growth factor receptor(EGFR)pathway and angiogenesis play important roles in glioma growth,invasion,and recurrence.The present study aimed to use proteomic methods to probe into the role of the EGF-EGFR-angiogenesis axis in the tumorigenesis of glioma and access the therapeutic efficacy of selumetinib on glioma.Methods:Proteomic profiling was used to characterize 200 paired EGFRpositive and EGFR-negative glioma tissues of all pathological types.The quantitative mass spectrometry data were used for systematic analysis of the proteomic profiles of 10 EGFR-positive and 10 EGFR-negative glioma cases.Consensusclustering analysis was used to screen target proteins.Immunofluorescence analysis,cell growth assay,and intracranial xenograft experiments were used to verify and test the therapeutic effect of selumetinib on glioma.Results:Advanced proteomic screening demonstrated that the expression of EGF-like domain multiple 7(EGFL7)was higher in EGFR-positive tumor tissues than in EGFR-negative tumor tissues.In addition,EGFL7 could act as an activatorin vitro and in vivo to promote glioma cell proliferation.EGFL7 was associated strongly with EGFR and prognosis.EGFL7 knockdown effectively suppressed glioma cell proliferation.Selumetinib treatment showed tumor reduction effect in EGFR-positive glioblastoma xenograft mouse model.Conclusions:EGFL7 is a potential diagnostic biomarker and therapeutic target of glioma.Selumetinib could target the EGFR pathway and possibly improve the prognosis of EGFR-positive glioma.
文摘Objective: To detect the expression and location of TGF-β1, ADAM12 and HB-EGF in primary hepatic carcinoma and study their effect on the growth and metastasis of hepatoma carcinoma cell. Methods: TGF-β1, ADAM12 and HB-EGF were detected by RT-PCR and immunohistochemistry in 30 cases of hepatic carcinoma tissues, 30 cases of adjacent carci- noma tissues and 5 cases of normal hepatic tissues. Results: RT-PCR analyses showed that the mRNA expression of TGF-β1, ADAM12 and HB-EGF were markedly increased in each hepatic carcinoma tissue compared with its adjacent tissue (P < 0.01), but no signal was detected in normal hepatic tissue. Immunohistochemistry showed the same outcome on the expression of above three factors in hepatic tissues as RT-PCR. Proteins location analyses showed the proteins of TGF-β1, ADAM12 and HB-EGF all distributed in the stroma of hepatic carcinoma tissues. The positive correlation was found between TGF-β1 and ADAM12 (r = 0.6137, P < 0.05), as well as ADAM12 and HB-EGF (r = 0.5763, P < 0.05). The protein expression of TGF-β1, ADAM12 and HB-EGF were correlated with the size of tumors, degree of differentiation of hepatoma carcinoma cells, portal vein thrombus and the metastasis of absorbent glands, especially with hepatic cirrhosis caused by hepatitis B virus. Conclu- sion: TGF-β1, ADAM12 and HB-EGF possibly play an important role in the process of growth, invasion and metastasis of hepatoma carcinoma cell, meanwhile, the above three factors may collectively participate in the transition from hepatic cirrhosis caused by hepatitis B virus to hepatocellular carcinoma.
