Plasma seprase and DPP4 levels as markers of disease and prognosis in cancer

Plasma seprase and DPP4 levels as markers of disease and prognosis in cancer
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DOI:
10.1155/2012/706745
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发表时间:
2012-01-01
期刊:
影响因子:
--
通讯作者:
Chen, Wen-Tien
Chen, Wen-Tien
中科院分区:
医学4区
文献类型:
--
作者:
Javidroozi, Mazyar;Zucker, Stanley;Chen, Wen-Tien

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Seprase(成纤维细胞活化蛋白a)已被研究为各种类型实体瘤的侵袭生物标志物。我们研究了癌症中seprase和同源蛋白酶DPP 4的血浆水平是否可以作为肿瘤生物标志物。我们开发了灵敏和特异性的酶联免疫吸附试验(ELISA)来测量这些蛋白酶。在747份血浆样本(来自139名健康志愿者和561名癌症患者)中,平均seprase和DPP 4水平分别为0.51 +/- 0.30和4.65 +/- 6.37 μ g/mL,并且它们彼此相关(R-2 = 0.382)。与健康受试者相比,癌症患者的血浆DPP 4和seprase水平显著较低(DPP 4为4.38 μ g/mL对5.65 μ g/mL,p < 0.001; seprase为0.46 μ g/mL对0.66 μ g/mL,p < 0.001)。在所有癌症组合(n = 346)以及头颈部恶性肿瘤(n = 38)中,较高的DPP 4与较好的生存率相关。在所有非转移性癌症(n = 151)以及头颈部恶性肿瘤中,较高的seprase与较好的生存率相关,但在结直肠癌中生存率较差(n = 47)。这项研究表明,与实体瘤中的高表达相反,seprase和DPP 4的血浆浓度降低,并且与大多数类型癌症的存活率呈负相关,表明这些循环蛋白酶代表有用的肿瘤标志物。
Seprase (fibroblast activation protein a) 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 mu g/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 mu g/mL, p < 0.001 for DPP4; 0.46 versus 0.66 mu g/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.