The role of interferon pathway in progression and metastasis in renal cell carcinoma

• Project/Area Number: 16591617
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: Dokkyo Medical University
• Principal Investigator: KAMAI Takao Dokkyo Medical University, Assistant professor, 医学部, 講師 (80316562)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,300,000 (Direct Cost: ¥3,300,000); Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000); Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
• Keywords: Renal cell carcinoma / interferon alpha receptor / mRNA / real time RT-PCR / metastasis / インターロイキン10 / インターフェロンαレセプター1型 / インターフェロンαレセプター2型 / real-time RT-PCR / western blotting / IFNAR1 / IFNAR2 / RT-PCR法 / 膀胱癌 / 精巣癌

Research Abstract

Interferon alpha receptor (IFNAR) 1 and IFNAR2 mRNAs were detected in tumor, and non-tumor kidney in 91 patients. There was no relation between the Tumor(T)/Nn-tumor(N) levels of mRNAs for IFNAR1 and grade. In contrast, increased T/N levels of mRNAs for IFNAR2 were associated with high grade differentiation and stage (P<0.0001).. The T/N level of IFNAR2 was higher in cancer with distant metastasis than in organ confined (P<0.0001)..
The protein of IFNAR2 were abundantly expressed in tumors with metastasis than those of organ confined in Western blotting (P<0.0001)
Cases were divided into two groups with expression above and below the mean of IFNAR1 and IFNAR2, high expression (IFNAR1 ; 41 patients, IFNAR2 ; 33 patients) and low expression (IFNAR1 ; 50 patients, IFNAR2 ; 58 patients). Comparison of Kaplan-Meier survival rate plots in patients with low vs. high expression of IFNAR2 linked high IFNAR2 expression with shortened overall survival (P<0.0001). Overall survival in univariate analysis in according to the Cox proportional hazards model was influenced significantly by grade, stage, metastasis, and IFNAR levels (P<0.01). By multivariate analysis, stage, metastasis, and IFNAR levels were an independent prognostic factor for overall survival (P<0.05).
Cases of tumors without distant metastasis at nephrectomy (M0 ; 64 patients) were divided into those with IRNAR2 expression above (25 patients) or below (39 patients) based on a mean of IFNAR. In these localized tumors, Kaplan-Meier plots showed that high T/N levels of IFNAR2 had a significant influence on recurrence-free survival (P=0.0112). Although stage and IFNAR2 predicted recurrence-free survival of localized cases in univariate analyses, only IFNAR2 remained significant in a multivariate analyses.
IFNAR1 was not related to disease-free survival in superficial tumors.