Haptoglobin Promoter Polymorphism Rs5472 As a Prognostic Biomarker for Peptide Vaccine Efficacy in Castration-resistant Prostate Cancer Patients

Overview

Journal Cancer Immunol Immunother

Specialties Allergy & Immunology
Oncology
Pharmacology

Date 2015 Oct 3

PMID 26428930

Citations 4

Authors

Hiromitsu Araki

Xiaoliang Pang

Nobukazu Komatsu

Mikiko Soejima

Nawoe Miyata

Mari Takaki

Shigeru Muta

Tetsuro Sasada

Masanori Noguchi

Yoshiro Koda

Kyogo Itoh

Satoru Kuhara

Kosuke Tashiro

Affiliations

Soon will be listed here.

Abstract

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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