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Correlation Research Of Golgi Phosphoprotein 2 (GOLPH2) Expression With Lung And Liver Cancer

Posted on:2011-03-05Degree:MasterType:Thesis
Country:ChinaCandidate:F F ZhangFull Text:PDF
GTID:2144360308455308Subject:Biochemistry and Molecular Biology
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1. Golgi Phosphoprotein 2 (GOLPH2) Expression in Lung cancerGolgi phosphoprotein 2 (GOLPH2; also known as GP73 and GOLM1) has been recently detected to be up-regulated in the tumor tissues of hepatocellular carcinoma (HCC), prostate cancer, renal cancer, as well as Alzheimer's and Wilson's diseases. It has also been proposed as a candidate serum marker for HCC. However, the status of GOLPH2 expression in lung cancer remains unknown.In this study, the GOLPH2 expression in lung cancer tissues were analyzed from the tumor tissue samples of 178 patients using immunohistochemistry. Levels of serum GOLPH2 from 133 lung cancer patients were also quantitatively compared with 70 healthy individuals by a sandwich enzyme-linked immunosorbent assay (ELISA). All adenocarcinoma (ADC) tissue samples (116, 100%) displayed strong staining, 97 (83.6%) of which displayed cytoplasmic diffused staining. However, for 49 squamous cell carcinoma samples, only 8 (16.3%) displayed strong staining intensity, including 2 (4.1%) cytoplasmic diffused staining. Statistically, GOLPH2 expression in tissues of ADC was significantly higher than in other types of lung cancer (P<0.001). The higher GOLPH2 expression in ADC was further confirmed in different types of lung cancer-derived cell line. Levels of serum GOLPH2 (sGOLPH2) were also detected. The mean value of sGOLPH2 concentration is 69 ng/ml in 133 lung cancer patients and 53 ng/ml in 70 healthy individuals. In conclusion, significantly elevated GOLPH2 expression was observed in ADC tumor tissues. The levels of sGOLPH2 were about 30% higher in lung cancer patients compared with healthy individuals.2. GOLPH2 Expression in Liver Cancer Xenograft Nude MouseGOLPH2 is a type II transmembrane glycoprotein with steady-state conditions, theoretically, seeming at first, an unlikely secretory protien. But, several following studies had proved levels of GOLPH2 in the sera (sGOLPH2) of patients with liver disease was increased and more than dozens of normal sera. Interestingly, serum GOLPH2 levels are upregulated during the progression of liver disease (for example from acute hepatitis to cirrhosis). That is, the more deterioration of liver cells in patients with lesions, the higher levels of GOLPH2 secretion. This suggests us that, the serum GOLPH2 levels are positive correlation with progression of liver disease. So we can quantitative monitor serum GOLPH2 to assess the degree of liver disease. However, human subjects have their limitations. The cell lines can not observe the long-term effects as well as simulated and replication in vivo environment.In this study, the human hepatoma HepG2 and Huh7 cells xenograft nude mice models were established. GOLPH2 expression in xenograft tumor was observed by immunohistochemistry, as well as levels of serum GOLPH2 were quantitation by sandwich ELISA. The results showed that, both HepG2 and Huh7 could secrete GOLPH2 into cell supernatant. However, HepG2 xenograft nude mice model serum unable detects GOLPH2, while the Huh7 xenograft nude mice model serum that can be detected. Comparing HE staining of tumor tissue, Huh7 formed tumor can prodigiously promote the angiogenesis, but HepG2 can not. Meanwhile, the result of Huh7 xenograft nude mice model serum GOLPH2 levels showed that serum GOLPH2 concentration increased with the tumor size. In conclusion, whether GOLPH2 could secrete into the serum is intimately related with angiogenesis. Simultaneously, the results confirmed GOLPH2 serum levels andwas positively related with tumor size, and from one side to reflect serum GOLPH2 may be positive related to the degree of cancerous cells.
Keywords/Search Tags:GOLPH2/GP73/GOLM1, Lung cancer, Adenocarcinoma, Tissue marker, Nude mouse, serum GOLPH2, Immunochemistry, Sandwich ELISA
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