Background Previous studies of prostate cancer autoantibodies have largely focused on diagnostic applications. So far, there have been no reports attempting to more comprehensively profile the landscape of prostate cancer-associated antibodies. Specifically, it is unknown whether the quantity of antibodies or the types of proteins recognized change with disease progression or treatment.
Methods A peptide microarray spanning the amino acid sequences of the gene products of 1611 prostate cancer-associated genes was synthesized. Serum samples from healthy male volunteers (n=15) and prostate cancer patients (n=85) were used to probe the array. These samples included patients with various clinical stages of disease: newly diagnosed localized prostate cancer, castration-sensitive non-metastatic prostate cancer (nmCSPC), castration-resistant non-metastatic prostate cancer (nmCRPC), and castration-resistant metastatic disease (mCRPC). Serial sera samples from individuals who received treatment with either standard androgen deprivation therapy (ADT) or an anti-tumor vaccine were also used to probe the array, to determine whether we could detect treatment-related changes.
Results We demonstrated that this peptide array yielded highly reproducible measurements of serum IgG levels. We found that the overall number of antibody responses did not increase with disease burden. However, the composition of recognized proteins shifted with clinical stage of disease. Our analysis revealed that the largest difference was between patients with castration-sensitive and castration-resistant disease. Patients with castration-resistant disease recognized more proteins associated with nucleic acid binding and gene regulation compared to men in other groups. Our longitudinal data showed that vaccine-treated patients developed increased responses to more proteins over the course of treatment than did ADT-treated patients, consistent with the development of antigen spread.
Conclusions This study represents the largest survey of prostate-cancer associated antibodies to date. We have been able to characterize the classes of proteins recognized by patients and determine how they change with disease burden. Our findings demonstrate the potential of this platform for measuring antigen spread and studying responses to immunomodulatory therapies.
Acknowledgements UW-Madison Medical Scientist Training Program: GM008692UW-Madison Institute for Clinical and Translational Research Predoctoral TL1 Program: TR002375
Ethics Approval Study protocols that permitted collection and use of human blood samples were reviewed and approved the University of Wisconsin Human Subjects’ Review Board (IRB). All patients gave written informed consent for use of blood products for research.
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