title: Haptoglobin promoter polymorphism rs5472 as a prognostic biomarker for peptide vaccine efficacy in castration-resistant prostate cancer patients.
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.
authors.affiliation: Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki Higashi-Ku, Fukuoka, 812-8581, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Araki
authors.affiliation: Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki Higashi-Ku, Fukuoka, 812-8581, Japan.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Pang
authors.affiliation: Department of Immunology and Immunotherapy, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Komatsu
authors.affiliation: Department of Forensic Medicine and Human Genetics, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
authors.forename: Mikiko
authors.initials: M
authors.lastname: Soejima
authors.affiliation: Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki Higashi-Ku, Fukuoka, 812-8581, Japan.
authors.forename: Nawoe
authors.initials: N
authors.lastname: Miyata
authors.affiliation: Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki Higashi-Ku, Fukuoka, 812-8581, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Takaki
authors.affiliation: Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki Higashi-Ku, Fukuoka, 812-8581, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Muta
authors.affiliation: Department of Immunology and Immunotherapy, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Sasada
authors.affiliation: Clinical Research Division of Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Noguchi
authors.affiliation: Department of Forensic Medicine and Human Genetics, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Koda
authors.affiliation: Cancer Vaccine Center, Kurume University, Kurume, Japan.
authors.forename: Kyogo
authors.initials: K
authors.lastname: Itoh
authors.affiliation: Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki Higashi-Ku, Fukuoka, 812-8581, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kuhara
authors.affiliation: Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki Higashi-Ku, Fukuoka, 812-8581, Japan. ktashiro@grt.kyushu-u.ac.jp.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Tashiro
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D006242:Haptoglobins / Q000235:genetics*; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D064129:Prostatic Neoplasms, Castration-Resistant / Q000175:diagnosis / Q000628:therapy*; D012333:RNA, Messenger / Q000235:genetics; D012189:Retrospective Studies; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000627:therapeutic use*
chemical_list: D014408:Biomarkers, Tumor; D019496:Cancer Vaccines; D006242:Haptoglobins; D012333:RNA, Messenger; D022223:Vaccines, Subunit
keywords: Biomarker; Castration-resistant prostate cancer; Haptoglobin; Peptide vaccine; SNP