2005 Fiscal Year Final Research Report Summary
The role of interferon pathway in progression and metastasis in renal cell carcinoma
Project/Area Number |
16591617
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Urology
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Research Institution | Dokkyo Medical University |
Principal Investigator |
KAMAI Takao Dokkyo Medical University, Assistant professor, 医学部, 講師 (80316562)
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Project Period (FY) |
2004 – 2005
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Keywords | Renal cell carcinoma / interferon alpha receptor / mRNA / real time RT-PCR / metastasis / インターロイキン10 |
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.
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