Circulating tumor-associated autoantibodies as novel diagnostic biomarkers in pancreatic adenocarcinoma

被引:6
作者
Zhuang, Liping [1 ,2 ,3 ]
Huang, Changjing [1 ,2 ,3 ]
Ning, Zhouyu [1 ,2 ,3 ]
Yang, Lina [1 ,2 ,3 ,4 ]
Zou, Wenbin [5 ]
Wang, Peng [1 ,2 ,3 ]
Cheng, Chien-Shan [1 ,2 ,3 ]
Meng, Zhiqiang [1 ,2 ,3 ]
机构
[1] Fudan Univ, Minimally Invas Therapy Ctr, Shanghai Canc Ctr, Shanghai, Peoples R China
[2] Fudan Univ, Shanghai Canc Ctr, Dept Integrat Oncol, Shanghai, Peoples R China
[3] Fudan Univ, Shanghai Med Coll, Dept Oncol, 270 DongAn Rd, Shanghai 200032, Peoples R China
[4] Qingdao Univ, Basic Med Coll, Dept Genet & Cell Biol, Qingdao, Shandong, Peoples R China
[5] Second Mil Med Univ, Dept Gastroenterol, Digest Endoscopy Ctr, Changhai Hosp, Shanghai, Peoples R China
关键词
circulating tumor-associated autoantibody; early diagnosis; pancreatic adenocarcinoma; proteome microarray; CONSENSUS STATEMENT; CANCER; SERUM; CA-19-9; PROGNOSIS; MARKERS; P53;
D O I
10.1002/ijc.34334
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
To develop a superior diagnostic approach for pancreatic adenocarcinoma (PAAC), the present study prospectively included 338 PAAC patients, 294 normal healthy volunteers (NHV), 122 chronic pancreatitis (CP) patients and 100 patients with non-PAAC malignancies. In the identification phase, HuProt Human Proteome Microarray, comprising 21 065 proteins, was used to identify serum tumor-associated autoantibodies (TAAbs) candidates differentiating PAAC (n = 30) from NHV (n = 30). A PAAC-focused array containing 165 differentially expressed TAAbs identified was subsequently adopted in the validation phase (n = 712) for specificity and sensitivities. The multivariate TAAbs signature for differentiation PAAC from controls (NHV + CP) identified five candidates, namely the IgG-type TAAbs against CLDN17, KCNN3, SLAMF7, SLC22A11 and OR51F2. Multivariate logistic performance model of y = (22.893 x CA19-9 + 0.68 x CLDN17 - 4.012) showed a significant better diagnostic accuracy than that of CA19-9 and CLDN17 in differentiating PAAC from controls (NHV + CP) (AUC = 0.97, 0.92 and 0.82, respectively, P-value < .0001). We further tested the autoantigen level of CLDN17 by ELISA in 82 sera samples from PAAC (n = 42), CP (n = 24) and NHV (n = 16). Similarly, the model showed superior diagnostic performance than that of CA19-9 and CLDN17 (AUC = 0.93, 0.83 and 0.81, respectively, P-value < .0001) in differentiating PAAC from controls. In conclusion, our study is the first to characterize the circulating TAAbs signatures in PAAC. The results showed that CLDN17 combined with CA19-9 provided potentially clinical value and may serve as noninvasive novel biomarkers for PAAC diagnosis.
引用
收藏
页码:1013 / 1024
页数:12
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