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).

CONCLUSION:

IFNAR2 is associated with the progression of RCC.

• Authors: Takao Kamai, Yoshiaki Yanai, Kyoko Arai, Hideyuki Abe, Tomonori Yamanishi, Masashi Kurimoto, Ken-Ichiro Yoshida
• Journal: BMC cancer (BMC Cancer) Vol. 7 Pg. 159 (Aug 15 2007) ISSN: 1471-2407 [Electronic] England
• PMID: 17697365 (Publication Type: Journal Article)

Chemical References

• IFNAR1 protein, human
• IFNAR2 protein, human
• Interferon-alpha
• RNA, Messenger
• Receptor, Interferon alpha-beta

Topics

• Adult
• Aged
• Aged, 80 and over
• Blotting, Western
• Carcinoma, Renal Cell (genetics, metabolism, secondary)
• Female
• Humans
• Interferon-alpha (pharmacology)
• Kidney Neoplasms (genetics, metabolism, pathology)
• Male
• Middle Aged
• Prognosis
• RNA, Messenger (genetics, metabolism)
• Receptor, Interferon alpha-beta (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Survival Rate