Increased interferon alpha receptor 2 mRNA levels is associated with renal cell carcinoma metastasis.
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.
Kamai
Takao
T
Department of Urology, Dokkyo Medical University, Tochigi, Japan. kamait@dokkyomed.ac.jp
Yanai
Yoshiaki
Y
Arai
Kyoko
K
Abe
Hideyuki
H
Yamanishi
Tomonori
T
Kurimoto
Masashi
M
Yoshida
Ken-Ichiro
K
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
C507964:IFNAR1 protein, human; C508033:IFNAR2 protein, human; D016898:Interferon-alpha; D012333:RNA, Messenger; D053633:Receptor, Interferon alpha-beta
Nat Rev Cancer. 2004 Feb;4(2):97-105
14964307
Clin Cancer Res. 2003 Jul;9(7):2632-41
12855641
J Pharmacol Toxicol Methods. 2004 Jul-Aug;50(1):59-66
15233969
Urol Clin North Am. 1993 May;20(2):303-21
8493752
Semin Oncol. 1995 Feb;22(1):42-60
7855619
N Engl J Med. 1996 Sep 19;335(12):865-75
8778606
Curr Probl Cancer. 1997 Jul-Aug;21(4):185-232
9285186
Br J Cancer. 1998;77(1):147-52
9459160
Oncol Rep. 1999 May-Jun;6(3):639-42
10203606
Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5007-12
10220409
Int J Cancer. 1999 May 31;81(5):682-7
10328216
Clin Cancer Res. 2005 Feb 1;11(3):1277-86
15709199
Br J Cancer. 2005 Sep 5;93(5):557-64
16106266
J Interferon Cytokine Res. 1999 Oct;19(10):1069-98
10547147
J Clin Oncol. 1999 Aug;17(8):2530-40
10561319
BJU Int. 2001 Feb;87(3):227-31
11167647
J Clin Oncol. 2002 Jan 1;20(1):289-96
11773181
J Urol. 2002 Aug;168(2):762-5
12131365
J Biol Chem. 2002 Sep 20;277(38):35635-41
12105218
J Urol. 2003 Feb;169(2):710-3
12544348
J Clin Oncol. 2003 Apr 1;21(7):1214-22
12663707
Dig Dis Sci. 2004 Feb;49(2):289-94
15104372