title: Increased interferon alpha receptor 2 mRNA levels is associated with renal cell carcinoma metastasis.
abstract: BACKGROUND
  Interferon-alpha (IFN-alpha) is one of the central agents in immunotherapy for renal cell carcinoma (RCC) and binds to the IFN-alpha receptor (IFNAR). We investigated the role of IFNAR in RCC.
  
  
  METHODS
  We quantified IFNAR mRNA expression in paired tumor and non-tumor samples from the surgical specimens of 103 consecutive patients with RCC using a real-time reverse transcription polymerase chain reaction (RT-PCR), and IFNAR2 protein using Western blotting.
  
  
  RESULTS
  The absolute level of IFNAR1 and IFNAR2 mRNAs in tumor and non-tumor tissues did not correlate with the malignant and metastatic profiles. The relative yields of the PCR product from the tumor tissue to that from the corresponding non-tumor tissue (T/N) for the expression of IFNAR mRNAs were calculated. While the T/N ratio of IFNAR1 did not correlate with any factor, a high T/N ratio of IFNAR2 correlated with poor differentiation (P < 0.05), local invasion (P < 0.001), and metastasis (P < 0.0001). By multivariate analysis, a high T/N ratio of IFNAR2 predicted a shortened overall survival in all cases (P < 0.05) and a shorter disease-free survival in those without metastasis (M0; 68 cases, P < 0.05). Impressively, patients with a poorer response to IFN-alpha treatment had a higher IFNAR2 T/N ratio than those who had a good response (P < 0.05). IFNAR2c protein expression was higher in the primary tumors in patients with metastases (M1; 35 cases) compared to those without ( P < 0.0001).
  
  
  CONCLUSIONS
  IFNAR2 is associated with the progression of RCC.
authors: Department of Urology, Dokkyo Medical University, Tochigi, Japan. kamait@dokkyomed.ac.jp
authors: Takao
authors: T
authors: Kamai
authors: Yoshiaki
authors: Y
authors: Yanai
authors: Kyoko
authors: K
authors: Arai
authors: Hideyuki
authors: H
authors: Abe
authors: Tomonori
authors: T
authors: Yamanishi
authors: Masashi
authors: M
authors: Kurimoto
authors: Ken-Ichiro
authors: K
authors: Yoshida
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D053633:Receptor, Interferon alpha-beta / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: C507964:IFNAR1 protein, human; C508033:IFNAR2 protein, human; D016898:Interferon-alpha; D012333:RNA, Messenger; D053633:Receptor, Interferon alpha-beta
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