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AZGP1 Autoantibody Predicts Survival and Histone Deacetylase Inhibitors Increase Expression in Lung Adenocarcinoma  Daniel L. Albertus, BS, Christopher.

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Presentation on theme: "AZGP1 Autoantibody Predicts Survival and Histone Deacetylase Inhibitors Increase Expression in Lung Adenocarcinoma  Daniel L. Albertus, BS, Christopher."— Presentation transcript:

1 AZGP1 Autoantibody Predicts Survival and Histone Deacetylase Inhibitors Increase Expression in Lung Adenocarcinoma  Daniel L. Albertus, BS, Christopher W. Seder, MD, Guoan Chen, MD, PhD, Xiaoju Wang, PhD, Wibisono Hartojo, MD, Lin Lin, MD, PhD, Amy Silvers, PhD, Daffyd G. Thomas, MD, PhD, Thomas J. Giordano, MD, PhD, Andrew C. Chang, MD, Mark B. Orringer, MD, William L. Bigbee, PhD, Arul M. Chinnaiyan, MD, PhD, David G. Beer, PhD  Journal of Thoracic Oncology  Volume 3, Issue 11, Pages (November 2008) DOI: /JTO.0b013e318189f5ec Copyright © 2008 International Association for the Study of Lung Cancer Terms and Conditions

2 FIGURE 1 Levels of AZGP1 autoantibody detected in (A) AD and (B) control subjects. The first 140 AD patients showed an autoantibody level of <2 whereas the first 139 control patients showed a level <2. A similar number of patients in each subset showed a level of AZGP1 autoantibody that was >2. AD, lung adenocarcinoma. Journal of Thoracic Oncology 2008 3, DOI: ( /JTO.0b013e318189f5ec) Copyright © 2008 International Association for the Study of Lung Cancer Terms and Conditions

3 FIGURE 2 A, Kaplan-Meier survival analysis for AZGP1 autoantibody in AD patients. Patients with high levels of AZGP1 autoantibody (level >median 1.02) had significantly better 5-year survival than patients with low levels of AZGP1 autoantibody (p = 0.002). B, Kaplan-Meier survival curve analysis for AZGP1 autoantibody production in patients with stage I and II AD. Patients with high levels (level >median 1.02) of autoantibody had significantly better 5-year survival than patients with low levels (p = 0.008). AD, lung adenocarcinoma. Journal of Thoracic Oncology 2008 3, DOI: ( /JTO.0b013e318189f5ec) Copyright © 2008 International Association for the Study of Lung Cancer Terms and Conditions

4 FIGURE 3 A, Verification of Kaplan-Meier survival analysis for AZGP1 autoantibody in AD patients. Patients with high levels of AZGP1 autoantibody (level >median 1.02) has significantly better 5-year survival than patients with low levels of autoantibody (p = 0.02). B, Verification of Kaplan-Meier survival analysis for AZGP1 autoantibody production in patients with stage I and II AD. Patients with high levels (level >median 1.02) of autoantibody had significantly better 5-year survival than patients with low levels (p = 0.036). AD, lung adenocarcinoma. Journal of Thoracic Oncology 2008 3, DOI: ( /JTO.0b013e318189f5ec) Copyright © 2008 International Association for the Study of Lung Cancer Terms and Conditions

5 FIGURE 4 Oligonucleotide microarray analysis of 86 AD and 10 normal samples revealed that 31.3% of adenocarcinomas expressed AZGP1 at least two fold more than the controls. Samples 1 to 86, AD; samples 87 to 96, controls. AD, lung adenocarcinoma. Journal of Thoracic Oncology 2008 3, DOI: ( /JTO.0b013e318189f5ec) Copyright © 2008 International Association for the Study of Lung Cancer Terms and Conditions

6 FIGURE 5 AZGP1 protein staining was not detected in (A) normal lung tissues, but was seen in (B) and (C) 42.8% of AD, and (D) 8.3% of SCC by immunohistochemistry. AD, lung adenocarcinoma; SCC, lung squamous cell carcinoma. Journal of Thoracic Oncology 2008 3, DOI: ( /JTO.0b013e318189f5ec) Copyright © 2008 International Association for the Study of Lung Cancer Terms and Conditions

7 FIGURE 6 A, Western blot demonstrating AZGP1 protein in the serum of all patients, irrespective of AZGP1 protein staining on tissue microarrays. AD, patient with lung adenocarcinoma; N, normal control subject; NE, no AZGP1 protein expression on TMA (negative); WE, weak AZGP1 expression (1+); IE, intermediate AZGP1 expression (2+); SE, strong AZGP1 expression (3+). B, Western blot demonstrating AZGP1 protein in the serum of all patients, irrespective of AZGP1 autoantibody production. AD, patient with lung adenocarcinoma; N, normal control subject; BL, patient with benign lung disease; Low, patient with serum autoantibody level < 2; High, patient with serum autoantibody level > 2. Journal of Thoracic Oncology 2008 3, DOI: ( /JTO.0b013e318189f5ec) Copyright © 2008 International Association for the Study of Lung Cancer Terms and Conditions

8 FIGURE 7 A, AZGP1 mRNA production is up-regulated in a time dependent manner by HDAC inhibitor TSA in A549 cells. Gene promoter demethylation by 5-AZA has no effect on AZGP1 mRNA expression in A549 and attenuates the up-regulation by TSA. B, AZGP1 mRNA production is up-regulated in a time dependent manner by HDAC inhibitor TSA in SKLU1 cells. Gene promoter demethylation by 5-AZA has no effect on AZGP1 mRNA expression in SKLU1 cells and attenuates the up-regulation by TSA. TSA, trichostatin A; 5-AZA, 5-aza-2’ deoxycytidine. *p < 0.05 with t test as compared with control. Journal of Thoracic Oncology 2008 3, DOI: ( /JTO.0b013e318189f5ec) Copyright © 2008 International Association for the Study of Lung Cancer Terms and Conditions

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