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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Authors | Nobutaka Furuya, Takao Kamai, Hiromichi Shirataki, Yoshiaki Yanai, Takehiko Fukuda, Tomoya Mizuno, Fumihiko Nakamura, Tsunehito Kambara, Kimihiro Nakanishi, Hideyuki Abe, Ken-Ichiro Yoshida |
Journal | Cancer immunology, immunotherapy : CII
(Cancer Immunol Immunother)
Vol. 60
Issue 6
Pg. 793-808
(Jun 2011)
ISSN: 1432-0851 [Electronic] Germany |
PMID | 21350947
(Publication Type: Journal Article)
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Chemical References |
- Benzenesulfonates
- IFNAR2 protein, human
- Interferon-alpha
- Phenylurea Compounds
- Pyridines
- RNA, Messenger
- Receptor, Interferon alpha-beta
- Niacinamide
- Sorafenib
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Antineoplastic Combined Chemotherapy Protocols
(administration & dosage)
- Benzenesulfonates
(administration & dosage)
- Carcinoma, Renal Cell
(blood, drug therapy, genetics, pathology)
- Female
- Humans
- Interferon-alpha
(administration & dosage)
- Kidney Neoplasms
(blood, drug therapy, genetics, pathology)
- Male
- Middle Aged
- Niacinamide
(analogs & derivatives)
- Phenylurea Compounds
- Prognosis
- Pyridines
(administration & dosage)
- RNA, Messenger
(blood, genetics, metabolism)
- Receptor, Interferon alpha-beta
(genetics)
- Reverse Transcriptase Polymerase Chain Reaction
- Sorafenib
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