4.7 Article

Identification of novel serological autoantibodies in Chinese prostate cancer patients using high-throughput protein arrays

Journal

CANCER IMMUNOLOGY IMMUNOTHERAPY
Volume 72, Issue 1, Pages 235-247

Publisher

SPRINGER
DOI: 10.1007/s00262-022-03242-0

Keywords

Prostate cancer; Diagnostic biomarker; Autoantibody; Gray-zone PSA; Protein array; Backpropagation artificial neural network

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This study provides a comprehensive profiling of autoantibodies in Chinese prostate cancer patients and identifies novel diagnostic autoantibody biomarkers, especially for the identification of gray-zone PSA patients.
Autoantibody (AAb) has a prominent role in prostate cancer (PCa), with few studies profiling the AAb landscape in Chinese patients. Therefore, the AAb landscape in Chinese patients was characterized using protein arrays. First, in the discovery phase, Huprot arrays outlined autoimmune profiles against similar to 21,888 proteins from 57 samples. In the verification phase, the PCa-focused arrays detected 25 AAbs selected from the discovery phase within 178 samples. Then, PCa was detected using a backpropagation artificial neural network (BPANN) model. In the validation phase, an enzyme-linked immunosorbent assay (ELISA) was used to validate four AAb biomarkers from 196 samples. Huprot arrays profiled distinct PCa, benign prostate diseases (BPD), and health AAb landscapes. PCa-focused array depicted that IFITS and CPDX AAbs could distinguish PCa from health with an area under curve (AUC) of 0.71 and 0.70, respectively. PAH and FCER2 AAbs had AUCs of 0.86 and 0.88 in discriminating PCa from BPD. Particularly, PAH AAb detected patients in the prostate-specific antigen (PSA) gray zone with an AUC of 0.86. Meanwhile, the BPANN model of 4-AAb (IFITS, PAH, FCER2, CPDX) panel attained AUC of 0.83 among the two cohorts for detecting patients with gray-zone PSA. In the validation cohort, the IFITS AAb was upregulated in PCa compared to health (p < 0.001). Compared with BPD, PAH and FCER2 AAbs were significantly elevated in PCa (p = 0 .012 and 0.039). We have demonstrated the first extensive profiling of autoantibodies in Chinese PCa patients, identifying novel diagnostic AAb biomarkers, especially for identification of gray-zone-PSA patients.

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