Affiliations: Department of Medicine, Stony Brook University, Stony
Brook, NY, USA | Department of Anesthesiology, Englewood Hospital and
Medical Center, Englewood, NJ, USA | Departments of Research and Medicine, Veterans Affairs
Medical Center, Northport, NY, USA
Note: [] Corresponding author: Mazyar Javidroozi, M.D., Ph.D., Department
of Anesthesiology, Englewood Hospital and Medical Center, 350 Engle Street,
Englewood, NJ 07631, USA. Tel.: +1 201 894 3917; Fax: +1 201 894 0585; E-mail:
mazyarjr@yahoo.com
Abstract: 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 (R^{2}= 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.
