Evaluation of the circulating level of fibroblast activation protein α for diagnosis of esophageal squamous cell carcinoma
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Yuehua Liao1,*, Shan Xing2,*, Banglao Xu3, Wanli Liu2, Ge Zhang1
1Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-Sen University, University Town, Guangzhou, China
2Department of Clinical Laboratory Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
3Department of Clinical Laboratory Medicine, Guangzhou First Municipal People’s Hospital, Guangzhou Medical University, Guangzhou, China
*These authors contributed equally to this work
Ge Zhang, email: [email protected]
Keywords: FAPα, esophageal squamous cell carcinoma, plasma, diagnosis biomarker, ELISA
Received: September 26, 2016 Accepted: March 09, 2017 Published: March 16, 2017
To evaluate whether circulating fibroblast activation protein α (FAPα) could serve as a biomarker for the diagnosis of esophageal squamous cell carcinoma (ESCC), enzyme-linked immunosorbent assay (ELISA) was used to detect plasma FAPα in 556 participants including ESCC group, benign esophageal disease group, healthy controls and other cancer controls group. The levels of plasma FAPα were significantly decreased in ESCC patients (P < 0.001) and showed a positive correlation with HDL-C levels (R = 0.372, P < 0.001). The sensitivity and specificity of plasma FAPα were 56.1% and 85.6% based on the optimal cut-off (49.04 ng/ml, AUC = 0.714). The combination of FAPα and the traditional biomarkers (CEA, CYFR211 and SCCA) improved the sensitivity (41.5%) without compromising the specificity (95.0%). Contradictorily, the immunohistochemical staining revealed the overexpression of FAPα in stroma of ESCC tissues. So the source of soluble FAPα was further explored by qRT-PCR, Western blotting, ELISA and immunoprecipitation in fibroblast cell lines and mouse xenograft models. We found that the plasma FAPα was not correlated with the FAPα expressed in tumor, and the multi-organ might contribute to the circulating levels of FAPα including skeletal muscle, liver and bone marrow. These results indicated that the low plasma FAPα level might due to the systemic reaction to the presence of tumor and circulating FAPα level might be a potential indicator for diagnosing ESCC.
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