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
N1 - Funding Information:
This study was supported in part by a research program of the Regional Innovation Cluster Program of the Ministry of Education, Culture, Sports, Science and Technology of Japan, Japan Agency for Medical Research and Development (AMED), and a grant from the Sendai Kousei Hospital.
Publisher Copyright:
© 2015, Springer-Verlag Berlin Heidelberg.
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.
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U2 - 10.1007/s00262-015-1756-7
DO - 10.1007/s00262-015-1756-7
M3 - Article
C2 - 26428930
AN - SCOPUS:84947047031
SN - 0340-7004
VL - 64
SP - 1565
EP - 1573
JO - Cancer Immunology, Immunotherapy
JF - Cancer Immunology, Immunotherapy
IS - 12
ER -
