Haptoglobin promoter polymorphism rs5472 as a prognostic biomarker for peptide vaccine efficacy in castration-resistant prostate cancer patients

Haptoglobin promoter polymorphism rs5472 as a prognostic biomarker for peptide vaccine efficacy in castration-resistant prostate cancer patients

Personalized peptide vaccination (PPV) is an attractive approach to cancer immunotherapy with strong immune-boosting effects conferring significant clinical benefit. However, as with most therapeutic agents, there is a difference in clinical efficacy among patients receiving PPV. Therefore, a useful...

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Bibliographic Details
Published in:Cancer Immunology, Immunotherapy Vol. 64; no. 12; pp. 1565 - 1573
Main Authors: Araki, Hiromitsu, Pang, Xiaoliang, Komatsu, Nobukazu, Soejima, Mikiko, Miyata, Nawoe, Takaki, Mari, Muta, Shigeru, Sasada, Tetsuro, Noguchi, Masanori, Koda, Yoshiro, Itoh, Kyogo, Kuhara, Satoru, Tashiro, Kosuke
Format: Journal Article
Language:English
Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-12-2015
Springer Nature B.V
Subjects:
Biomarkers
Biomarkers, Tumor - genetics
Cancer Research
Cancer therapies
Cancer vaccines
Cancer Vaccines - therapeutic use
Clinical outcomes
Disease
Gene expression
Glycoproteins
Haptoglobins - genetics
Humans
Immunology
Immunotherapy
Male
Medicine
Medicine & Public Health
Oncology
Original
Original Article
Peptides
Polymorphism
Polymorphism, Genetic
Promoter Regions, Genetic - genetics
Prostate cancer
Prostatic Neoplasms, Castration-Resistant - diagnosis
Prostatic Neoplasms, Castration-Resistant - therapy
Retrospective Studies
RNA, Messenger - genetics
Treatment Outcome
Vaccines, Subunit - therapeutic use
Japan
Castration-resistant prostate cancer
Biomarker
Peptide vaccine
Haptoglobin
SNP
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Description
Summary:Personalized peptide vaccination (PPV) is an attractive approach to cancer immunotherapy with strong immune-boosting effects conferring significant clinical benefit. However, as with most therapeutic agents, there is a difference in clinical efficacy among patients receiving PPV. Therefore, a useful biomarker is urgently needed for prognosticating clinical outcomes to preselect patients who would benefit the most from PPV. In this retrospective study, to detect a molecular prognosticator of clinical outcomes for PPV, we analyzed whole-genome gene expression profiles of peripheral blood mononuclear cells (PBMCs) in castration-resistant prostate cancer (CRPC) patients before administration of PPV. Cox regression analysis revealed that mRNA expression of myeloperoxidase, haptoglobin, and neutrophil elastase was significantly associated with overall survival (OS) among vaccinated CRPC patients (adjusted P  < 0.01). By promoter sequence analysis of these three genes, we found that rs5472 of haptoglobin ( HP ), an acute-phase plasma glycoprotein, was strongly correlated to OS of vaccinated CRPC patients ( P  = 0.0047, hazard ratio 0.47; 95 % confidence interval 0.28–0.80). Furthermore, both HP mRNA expression in PBMCs and protein level in plasma of CRPC patients before administration of PPV exhibited rs5472 dependence ( P  < 0.001 for mRNA expression and P  < 0.05 for protein level). Our findings suggest that rs5472 may play an important role in the immune response to PPV via regulation of HP . Thus, we concluded that rs5472 is a potential prognostic biomarker for PPV.
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ISSN:0340-7004
1432-0851
DOI:10.1007/s00262-015-1756-7