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

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

研究成果: ジャーナルへの寄稿記事

2 引用 (Scopus)

抄録

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.

元の言語英語
ページ(範囲)1565-1573
ページ数9
ジャーナルCancer Immunology, Immunotherapy
64
発行部数12
DOI
出版物ステータス出版済み - 12 1 2015

Fingerprint

Subunit Vaccines
Haptoglobins
Castration
Prostatic Neoplasms
Vaccination
Biomarkers
Peptides
Messenger RNA
Blood Cells
Leukocyte Elastase
Survival
Acute-Phase Proteins
Transcriptome
Immunotherapy
Peroxidase
Sequence Analysis
Blood Proteins
Retrospective Studies
Regression Analysis
Genome

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

これを引用

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

:: Cancer Immunology, Immunotherapy, 巻 64, 番号 12, 01.12.2015, p. 1565-1573.

研究成果: ジャーナルへの寄稿記事

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. / Haptoglobin promoter polymorphism rs5472 as a prognostic biomarker for peptide vaccine efficacy in castration-resistant prostate cancer patients. :: Cancer Immunology, Immunotherapy. 2015 ; 巻 64, 番号 12. pp. 1565-1573.
@article{3a9ab6ac44e741c3ba9c6a86545e713d,
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.",
author = "Hiromitsu Araki and Xiaoliang Pang and Nobukazu Komatsu and Mikiko Soejima and Nawoe Miyata and Mari Takaki and Shigeru Muta and Tetsuro Sasada and Masanori Noguchi and Yoshiro Koda and Kyogo Itoh and Satoru Kuhara and Kosuke Tashiro",
year = "2015",
month = "12",
day = "1",
doi = "10.1007/s00262-015-1756-7",
language = "English",
volume = "64",
pages = "1565--1573",
journal = "Cancer Immunology and Immunotherapy",
issn = "0340-7004",
publisher = "Springer Science and Business Media Deutschland GmbH",
number = "12",

}

TY - JOUR

T1 - Haptoglobin promoter polymorphism rs5472 as a prognostic biomarker for peptide vaccine efficacy in castration-resistant prostate cancer patients

AU - Araki, Hiromitsu

AU - Pang, Xiaoliang

AU - Komatsu, Nobukazu

AU - Soejima, Mikiko

AU - Miyata, Nawoe

AU - Takaki, Mari

AU - Muta, Shigeru

AU - Sasada, Tetsuro

AU - Noguchi, Masanori

AU - Koda, Yoshiro

AU - Itoh, Kyogo

AU - Kuhara, Satoru

AU - Tashiro, Kosuke

PY - 2015/12/1

Y1 - 2015/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84947047031&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84947047031&partnerID=8YFLogxK

U2 - 10.1007/s00262-015-1756-7

DO - 10.1007/s00262-015-1756-7

M3 - Article

C2 - 26428930

AN - SCOPUS:84947047031

VL - 64

SP - 1565

EP - 1573

JO - Cancer Immunology and Immunotherapy

JF - Cancer Immunology and Immunotherapy

SN - 0340-7004

IS - 12

ER -