AIM:To investigate the expression and clinical relevance of inhibitor of differentiation(ID)proteins in biliary tract cancer.METHODS:ID protein expression was analyzed in129 samples from patients with advanced biliary...AIM:To investigate the expression and clinical relevance of inhibitor of differentiation(ID)proteins in biliary tract cancer.METHODS:ID protein expression was analyzed in129 samples from patients with advanced biliary tract cancer(BTC)(45 extrahepatic,50 intrahepatic,and 34 gallbladder cancers),compared to normal controls and correlated with clinical an pathological parameters.RESULTS:ID1-3 proteins are frequently overexpressed in all BTC subtypes analyzed.No correlation between increased ID protein expression and tumor grading,tumor subtype or treatment response was detected.Survival was influenced primary tumor localization(extrahepatic vs intrahepatic and gall bladder cancer,OS 1.5 years vs 0.9 years vs 0.7 years,P=0.002),by stage at diagnosis(OS 2.7 years in stageⅠv s 0.6 years in stageⅣ,P<0.001),resection status and response to systemic chemotherapy.In a multivariate model,ID protein expression did not correlate with clinical prognosis.Nevertheless,there was a trend of shorter OS in patients with loss of cytoplasmic ID4 protein expression(P=0.076).CONCLUSION:ID protein expression is frequently deregulated in BTC but does not influence clinical prognosis.Their usefulness as prognostic biomarkers in BTC is very limited.展开更多
The formation of osteolytic bone lesions is a key process for osteolytic cancer to metastasize to the bone and is under the control of a set of transcription factors. Recently, the inhibitor of differentiation 1 (Id1...The formation of osteolytic bone lesions is a key process for osteolytic cancer to metastasize to the bone and is under the control of a set of transcription factors. Recently, the inhibitor of differentiation 1 (Id1) has been linked with angiogenesis, tumorigenesis, metastasis and bone formation. However, the function of Id1 during the process of bone destruction caused by cancer in vivo has not yet been elucidated. We, therefore, examined whether and how Id1 affects the ability of cancer to form osteolytic lesion in vivo. The study used a lentiviral vector overexpressing short hairpin RNA (shRNA) targeting Id1 gene. PC3 cells, a prostate cancer cell line, were transduced with Id1 shRNA or negative control (NC) shRNA before implantation in BALB/c mice. Cells were implanted in a tibial injection model. Tumor formation in bone was monitored by X-ray. The relationship between parathyroid hormone-related protein (PTHrP), an osteolytic factor, and Id1 was analyzed by using immunohistochemistry in tissue sections from osteolytic lesion of the BALB/c mice. Our results showed that Id1 shRNA delivery to PC3 cells by lentivirus caused efficient and stable Id1 gene silencing. In the intratibial model, PC3 cells produced primarily osteolytic lesions in the bone. Eleven of 14 mice in Id1 shRNA group but only 4 of 14 mice in the NC shRNA group developed osteolytic lesions with cortical destruction at 4th week. Mice treated with Id1 shRNA had larger tumor volume in the bone and larger cortical destruction. The expression of PTHrP protein in PC3 cells was not affected by Id1 knockdown in vivo. These results indicate that Id1 may down-regulate the ability of PC3 cells to form osteolytic lesions in vivo and the signal pathway needs to be further investigated.展开更多
文摘AIM:To investigate the expression and clinical relevance of inhibitor of differentiation(ID)proteins in biliary tract cancer.METHODS:ID protein expression was analyzed in129 samples from patients with advanced biliary tract cancer(BTC)(45 extrahepatic,50 intrahepatic,and 34 gallbladder cancers),compared to normal controls and correlated with clinical an pathological parameters.RESULTS:ID1-3 proteins are frequently overexpressed in all BTC subtypes analyzed.No correlation between increased ID protein expression and tumor grading,tumor subtype or treatment response was detected.Survival was influenced primary tumor localization(extrahepatic vs intrahepatic and gall bladder cancer,OS 1.5 years vs 0.9 years vs 0.7 years,P=0.002),by stage at diagnosis(OS 2.7 years in stageⅠv s 0.6 years in stageⅣ,P<0.001),resection status and response to systemic chemotherapy.In a multivariate model,ID protein expression did not correlate with clinical prognosis.Nevertheless,there was a trend of shorter OS in patients with loss of cytoplasmic ID4 protein expression(P=0.076).CONCLUSION:ID protein expression is frequently deregulated in BTC but does not influence clinical prognosis.Their usefulness as prognostic biomarkers in BTC is very limited.
基金supported by a grant from the National Natural Science Foundation of China(No.30772206)
文摘The formation of osteolytic bone lesions is a key process for osteolytic cancer to metastasize to the bone and is under the control of a set of transcription factors. Recently, the inhibitor of differentiation 1 (Id1) has been linked with angiogenesis, tumorigenesis, metastasis and bone formation. However, the function of Id1 during the process of bone destruction caused by cancer in vivo has not yet been elucidated. We, therefore, examined whether and how Id1 affects the ability of cancer to form osteolytic lesion in vivo. The study used a lentiviral vector overexpressing short hairpin RNA (shRNA) targeting Id1 gene. PC3 cells, a prostate cancer cell line, were transduced with Id1 shRNA or negative control (NC) shRNA before implantation in BALB/c mice. Cells were implanted in a tibial injection model. Tumor formation in bone was monitored by X-ray. The relationship between parathyroid hormone-related protein (PTHrP), an osteolytic factor, and Id1 was analyzed by using immunohistochemistry in tissue sections from osteolytic lesion of the BALB/c mice. Our results showed that Id1 shRNA delivery to PC3 cells by lentivirus caused efficient and stable Id1 gene silencing. In the intratibial model, PC3 cells produced primarily osteolytic lesions in the bone. Eleven of 14 mice in Id1 shRNA group but only 4 of 14 mice in the NC shRNA group developed osteolytic lesions with cortical destruction at 4th week. Mice treated with Id1 shRNA had larger tumor volume in the bone and larger cortical destruction. The expression of PTHrP protein in PC3 cells was not affected by Id1 knockdown in vivo. These results indicate that Id1 may down-regulate the ability of PC3 cells to form osteolytic lesions in vivo and the signal pathway needs to be further investigated.