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Disease Markers
Volume 32 (2012), Issue 5, Pages 309-320

Plasma Seprase and DPP4 Levels as Markers of Disease and Prognosis in Cancer

Mazyar Javidroozi,1,2 Stanley Zucker,1,3 and Wen-Tien Chen1

1Department of Medicine, Stony Brook University, Stony Brook, NY, USA
2Department of Anesthesiology, Englewood Hospital and Medical Center, Englewood, NJ, USA
3Departments of Research and Medicine, Veterans Affairs Medical Center, Northport, NY, USA

Received 7 March 2012; Accepted 7 March 2012

Copyright © 2012 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Seprase (fibroblast activation protein α) has been examined as an invasion biomarker for various types of solid tumors. We studied whether plasma levels of seprase and homologous protease, DPP4 in cancer might serve as tumor biomarkers. We developed sensitive and specific Enzyme-Linked Immunosorbent Assays (ELISAs) to measure these proteases. In 747 plasma samples (from 139 healthy volunteers and 561 cancer patients), mean seprase and DPP4 levels were 0.51 ± 0.30 and 4.65 ± 6.37 μg/mL, respectively, and they were correlated with each other (R2 = 0.382). Plasma DPP4 and seprase levels were significantly lower in cancer patients compared with healthy subjects (4.38 versus 5.65 μg/mL, p < 0.001 for DPP4; 0.46 versus 0.66 μg/mL, p < 0.001 for seprase). Higher DPP4 was associated with better survival in all cancers combined (n = 346) as well as in head and neck malignancies (n = 38). Higher seprase was associated with better survival in all non-metastatic cancers combined (n = 151) as well as head and neck malignancies, but worse survival in colorectal cancers (n = 47). This study demonstrates that in contrast to the high expression in solid tumors, plasma concentrations of seprase and DPP4 are reduced and correlate inversely with survival in most types of cancer, suggesting that these circulating proteases represent useful tumor markers.