title: The clinical performance evaluation of novel protein chips for eleven biomarkers detection and the diagnostic model study.
abstract: We aimed to develop and validate two novel protein chips, which are based on microarray chemiluminescence immunoassay and can simultaneously detected 11 biomarkers, and then to evaluate their clinical diagnostic value by comparing with the traditional methods. Protein chips were evaluated for limit of detection, specificity, common interferences, linearity, precision and accuracy. 11 biomarkers were simultaneously detected by traditional methods and protein chips in 3683 samples, which included 1723 cancer patients, 1798 benign diseases patients and 162 healthy controls. After assay validation, protein chips demonstrated high sensitivity, high specificity, good linearity, low imprecision and were free of common interferences. Compared with the traditional methods, protein chips have good correlation in the detection of all the 13 kinds of biomarkers (r≥0.935, P<0.001). For specific cancer detection, there were no statistically significant differences between the traditional method and novel protein chips, except that male protein chip showed significantly better diagnostic value on NSE detection (P=0.004) but significantly worse value on pro-GRP detection (P=0.012), female chip showed significantly better diagnostic value on pro-GRP detection (P=0.005). Furthermore, both male and female multivariate diagnostic models had significantly better diagnostic value than single detection of PGI, PG II, pro-GRP, NSE and CA125 (P<0.05). In addition, male models had significantly better diagnostic value than single CA199 and free-PSA (P<0.05), while female models observed significantly better diagnostic value than single CA724 and β-HCG (P<0.05). For total disease or cancer detection, the AUC of multivariate logistic regression for the male and female disease detection was 0.981 (95% CI: 0.975-0.987) and 0.836 (95% CI: 0.798-0.874), respectively. While, that for total cancer detection was 0.691 (95% CI: 0.666-0.717) and 0.753 (95% CI: 0.731-0.775), respectively. The new designed protein chips are simple, multiplex and reliable clinical assays and the multi-parameter diagnostic models based on them could significantly improve their clinical performance.
authors.affiliation: Core Laboratory of Translational Medicine, State Key Laboratory of Kidney Disease, Chinese PLA General Hospital Beijing, P. R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Interventional Therapy Department, Peking University Cancer Hospital&Institute Beijing, P. R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Interventional Therapy Department, Peking University Cancer Hospital&Institute Beijing, P. R. China.
authors.forename: Pengjun
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Diagnosis, Changhai Hospital, The Second Military Medical University Shanghai, P. R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Shen
authors.affiliation: Core Laboratory of Translational Medicine, State Key Laboratory of Kidney Disease, Chinese PLA General Hospital Beijing, P. R. China.
authors.forename: Zi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Clinical Biochemistry, Chinese PLA General Hospital Beijing, P. R. China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Wen
authors.affiliation: Department of Clinical Biochemistry, Chinese PLA General Hospital Beijing, P. R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Clinical Biochemistry, Chinese PLA General Hospital Beijing, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Clinical Biochemistry, Chinese PLA General Hospital Beijing, P. R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Dong
authors.affiliation: Core Laboratory of Translational Medicine, State Key Laboratory of Kidney Disease, Chinese PLA General Hospital Beijing, P. R. China.
authors.forename: Caie
authors.initials: C
authors.lastname: Yang
authors.affiliation: Jiangsu Sunlant Bioengineering Co., Ltd Wuxi, P. R. China.
authors.forename: Tangming
authors.initials: T
authors.lastname: Wu
authors.affiliation: Jiangsu Sunlant Bioengineering Co., Ltd Wuxi, P. R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Core Laboratory of Translational Medicine, State Key Laboratory of Kidney Disease, Chinese PLA General Hospital Beijing, P. R. China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Tian
keywords: Cancer biomarkers; ROC curve; diagnostic tests; early detection of cancer; logistic models; protein array analysis