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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 6/2011

Open Access 01-06-2011 | Original article

Serum interferon alpha receptor 2 mRNA may predict efficacy of interferon alpha with/without low-dose sorafenib for metastatic clear cell renal cell carcinoma

Authors: Nobutaka Furuya, Takao Kamai, Hiromichi Shirataki, Yoshiaki Yanai, Takehiko Fukuda, Tomoya Mizuno, Fumihiko Nakamura, Tsunehito Kambara, Kimihiro Nakanishi, Hideyuki Abe, Ken-Ichiro Yoshida

Published in: Cancer Immunology, Immunotherapy | Issue 6/2011

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Abstract

Background

Interferon (IFN) alpha is one of the central agents in immunotherapy for renal cell carcinoma (RCC). It acts by binding to the IFN-alpha receptor (IFNAR). We previously reported that increased tumor expression of IFNAR2 mRNA was associated with the metastatic potential and progression of RCC, as well as with a poor response of metastatic RCC to IFN-alpha therapy. This study investigated the influence of serum IFNAR2 in RCC patients.

Methods

We measured serum IFNAR2 mRNA levels and quantified IFNAR mRNA expression in paired tumor and non-tumor tissues from the surgical specimens of 66 consecutive RCC patients by the real-time reverse transcription polymerase chain reaction (RT-PCR). We also measured phosphorylated Akt (Ser-473) and phosphorylated-S6 ribosomal protein (Ser-235/236) proteins levels in paired tumor and non-tumor tissues of patients with metastatic RCC by Western blotting.

Results

The serum level of IFNAR2 mRNA was not associated with its tumor tissue level. Serum IFNAR2 mRNA was positively correlated with tumor size (P < 0.05), but not with tumor grade, pT stage, metastasis, microscopic vascular invasion, or serum C-reactive protein. Serum levels of IFNAR2 mRNA were significantly higher in patients with a good response to IFN-alpha ± sorafenib than in those with a poor response (P < 0.0001). Tumor tissue IFNAR2 mRNA levels and phosphorylated-S6 ribosomal protein (Ser-235/236) levels were associated with metastatic potential (P < 0.001 and P < 0.01, respectively), and patients with a low IFNAR2 mRNA level and low phosphorylated Akt (Ser-473) protein level in the primary tumor showed a good response to IFN-α ± sorafenib (IFN-α ± Sor: CR-PR) (P < 0.01 and P < 0.05, respectively). Kaplan–Meier survival analysis showed that a higher serum IFNAR2 mRNA level was associated with longer overall survival of treated patients (P < 0.05), while a higher tumor tissue IFNAR2 mRNA level was related to shorter overall survival (P < 0.01).

Conclusions

Our findings suggest that a high serum level of IFNAR2 mRNA may be a useful marker for predicting the response of metastatic RCC to IFN-alpha ± sorafenib therapy.
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Metadata
Title
Serum interferon alpha receptor 2 mRNA may predict efficacy of interferon alpha with/without low-dose sorafenib for metastatic clear cell renal cell carcinoma
Authors
Nobutaka Furuya
Takao Kamai
Hiromichi Shirataki
Yoshiaki Yanai
Takehiko Fukuda
Tomoya Mizuno
Fumihiko Nakamura
Tsunehito Kambara
Kimihiro Nakanishi
Hideyuki Abe
Ken-Ichiro Yoshida
Publication date
01-06-2011
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 6/2011
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-011-0989-3

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