STAT3 Polymorphism Can Predict the Response to Interferon-α Therapy in Patients with Metastatic Renal Cell Carcinoma

被引：26

作者：

Eto, Masatoshi ^{[1
,2
]}

Kamba, Tomomi ^{[3
]}

Miyake, Hideaki ^{[4
]}

Fujisawa, Masato ^{[4
]}

Kamai, Takao ^{[5
]}

Uemura, Hirotsugu ^{[6
]}

Tsukamoto, Taiji ^{[7
]}

Azuma, Haruhito ^{[8
]}

Matsubara, Akio ^{[9
]}

Nishimura, Kazuo ^{[10
]}

Nakamura, Tsuyoshi ^{[11
]}

Ogawa, Osamu ^{[3
]}

Naito, Seiji ^{[1
]}

机构：

[1] Kyushu Univ, Grad Sch Med Sci, Dept Urol, Fukuoka 812, Japan

[2] Kumamoto Univ, Dept Urol, Fac Life Sci, Kumamoto, Japan

[3] Kyoto Univ, Grad Sch Med, Dept Urol, Kyoto, Japan

[4] Kobe Univ, Grad Sch Med, Dept Surg Related, Div Urol, Kobe, Hyogo 657, Japan

[5] Dokkyo Med Univ, Dept Urol, Mibu, Tochigi, Japan

[6] Kinki Univ, Sch Med, Dept Urol, Osaka 589, Japan

[7] Sapporo Med Univ, Dept Urol Surg & Androl, Sch Med, Sapporo, Hokkaido, Japan

[8] Osaka Med Coll, Dept Urol, Takatsuki, Osaka 569, Japan

[9] Hiroshima Univ, Dept Urol, Grad Sch Biomed Sci, Hiroshima, Japan

[10] Osaka Med Ctr Canc & Cardiovasc Dis, Dept Urol, Osaka, Japan

[11] Nagasaki Univ, Fac Environm Studies, Nagasaki 852, Japan

来源：

EUROPEAN UROLOGY | 2013年 / 63卷 / 04期

关键词：

Interferon-alpha; Renal cell carcinoma; Single nucleotide polymorphisms; STAT3; IMMUNE-RESPONSES; CANCER; SUNITINIB; PATHWAY;

D O I：

10.1016/j.eururo.2012.09.052

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Background: In our 2007 retrospective study, we reported that single nucleotide polymorphisms (SNPs) in the signal transducer and activator of transcription 3 (acute-phase response factor) (STAT3) gene were significantly associated with better response to interferon (IFN)-alpha in patients with metastatic renal cell carcinoma (mRCC). Objective: To prospectively confirm those results, the Japan Immunotherapy SNPs-Study Group for Kidney Cancer conducted this trial. Design, setting, and participants: In this multicenter, prospective study, 203 eligible patients were enrolled. We evaluated the correlation between the antitumor effects of IFN-alpha and 11 SNPs (STAT3-2, STAT3-0, SOCS3-1, IL4R-34, PTGS1-3, PTGS1-4, PTGS1-5, PTGS2-12, IRF2-67, ICSBP-38, and TAP2-5) in eight genes in 180 patients who received IFN-alpha for >12 wk. Interventions: Patients were treated with three doses per week of IFN-alpha 5 million IU. Outcome measurements and statistical analysis: We analyzed the association of response to IFN-alpha and overall survival (OS) with genetic polymorphisms using a chi-square test and a logistic regression model. Results and limitations: The response rate of IFN-alpha was 13.8% (28 of 203 patients; 9 complete responses [CRs], 19 partial responses [PRs]). The CR rate of 4.4% was higher than we expected. Response to IFN-alpha was not associated with any of the 11 SNPs examined. However, when we assessed patients with CR, PR, and stable disease >24 wk as a group representing those with clinical response, a significant association was observed between STAT3-2 (rs1905341) and the clinical response of IFN-alpha (p = 0.039). Namely, C/C genotype of STAT3-2 was significantly associated with the clinical response of IFN-alpha and OS. These results were generated in Japanese patients and should be studied in other ethnic groups. Conclusions: This is the first prospective study demonstrating that a STAT3 polymorphism can be a predictive marker for treatment with IFN-alpha for patients with mRCC. (c) 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

引用

页码：745 / 752

页数：8

共 30 条

[21] Prognosis of Japanese Metastatic Renal Cell Carcinoma Patients in the Cytokine Era: A Cooperative Group Report of 1463 Patients [J].