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GP88 (progranulin): a novel tissue and circulating biomarker for non-small cell lung carcinoma.

Significance statement:

This paper demonstrates that measuring the tumor tissue expression of GP88/Progranulin by immunohistochemistry using anti-GP88/PGRN 6B3 antibody provides information on the risk of recurrence and death of patients with non-small cell lung carcinoma (early and advanced NSCLC stages). High GP88 IHC tissue score is associated with a decrease in progression-free survival. In addition, patients with advanced stage NSCLC have an elevated level of circulating GP88 measured by GP88/PGRN ELISA test when compared to non-lung cancer subjects.

 

GP88 (progranulin): a novel tissue and circulating biomarker for non-small cell lung carcinoma.. Global Medical Discovery

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Edelman MJ1, Feliciano J1, Yue B2, Bejarano P3, Ioffe O4, Reisman D5, Hawkins D6, Gai Q1, Hicks D2, Serrero G7. Hum Pathol. 2014 Sep;45(9):1893-9.

1Department of Medicine, University of Maryland School of Medicine, Greenebaum Cancer Center, Baltimore, MD 21201.and

2A&G Pharmaceutical, Columbia MD 21045.and

3Department of Pathology, Cleveland Clinic Florida, Weston, FL 33331.and

4Department of Pathology, University of Maryland School of Medicine, Greenebaum Cancer Center, Baltimore MD 21201.and

5Department of Medicine, University of Florida, Gainesville, FL 32610.and

6School of Statistics University of Minnesota, Minneapolis, MN 55455.and

7A&G Pharmaceutical, Columbia MD 21045; University of Maryland, Greenebaum Cancer Center, Baltimore, MD 21201. Electronic address: [email protected]

 

Abstract

GP88 (progranulin) is a growth and survival factor implicated in tumorigenesis and drug resistance. Previous studies showed that GP88 was expressed in breast cancer tissue in inverse correlation with survival. This study evaluates GP88 tissue expression in localized/locally advancedlung cancer and GP88 serum levels in advanced disease. GP88 expression was determined by immunohistochemistry in tumor tissue from non-small cell lung  carcinoma  (NSCLC) patients, 85 with localized (stage I-II), and 40 with locally advanced disease (stage IIIa) and correlated with clinical outcome. Serum GP88 levels from stage IIIb/IV patients, quantified by enzyme immunoassay were compared with GP88 levels from patients with chronic obstructive pulmonary disease and healthy individuals. GP88 was expressed in more than 80% adenocarcinoma  and squamous cell carcinoma in contrast to normal lung or small cell lung cancer. There was a statistically significant inverse association of GP88 expression (GP88 immunohistochemistry score, 3+ versus < 3+) with survival for patients with localized resected NSCLC with hazard ratio (HR) = 2.28 (P = .0076) for disease-free survival and HR = 2.17 (P = .014) for overall survival. A statistically significant decrease in progression-free survival (HR = 2.9; P = .022) for GP88 scores of 3+ versus less than 3+ was observed for stage IIIa after chemoradiotherapy. In addition, serum GP88 was significantly elevated in stage IIIb/IV NSCLC compared with control subjects (49.9 ng/mL versus 28.4 ng/mL; P < .0001). This is the first study demonstratingGP88 tissue and serum expression as a prognostic biomarker in localized and advanced disease. Future research will determine utility of monitoringGP88 and the potential of GP88 expression as a predictive marker for anti-GP88 therapeutics.

Copyright © 2014 Elsevier Inc. All rights reserved.

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