Prognostic Value of SETD2 Expression in Patients with Metastatic Renal Cell Carcinoma Treated with Tyrosine Kinase Inhibitors

详细信息    查看全文

• 作者：Jiajun Wang^a ; ^&lowast ; ; Li Liu^a ; ^&lowast ; ; Yang Qu^a ; ^&lowast ; ; Wei Xi^a ; Yu Xia^a ; Qi Bai^a ; Ying Xiong^a ; Qilai Long^a ; Jiejie Xu^b ; ^{jjxufdu@fudan.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Jianming Guo^a ; ^{guo.jianming@zs-hospital.sh.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：carcinoma ; renal cell ; neoplasm metastasis ; survival ; disease-free survival ; biomarkers
• 刊名：The Journal of Urology
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：196
• 期：5
• 页码：1363-1370
• 全文大小：1611 K

文摘

Mutations of SETD2 occur in 3% to 16% of clear cell renal cell carcinoma cases. Previous studies identified an association between SETD2 mutation and prognosis of patients with nonmetastatic clear cell renal cell carcinoma. In this study we explored the prognostic and predictive value of SETD2 expression in patients with metastatic renal cell carcinoma treated with targeted therapy.

Materials and Methods

We retrospectively enrolled 138 patients with metastatic renal cell carcinoma treated with sunitinib or sorafenib at a single institution from 2007 to 2014. SETD2 expression was assessed by immunohistochemistry on tissue microarrays.

Results

After excluding those patients with loss of followup or unavailable tissue samples, 111 were included in the study. Low SETD2 expression was associated with reduced overall survival (p <0.001) and progression-free survival (p=0.001). After adjustment for histological type, Heng risk group and drugs used for targeted therapy, SETD2 was defined as an independent prognostic marker for overall survival (HR 2.535 [95% CI 1.429–4.497], p=0.001) and progression-free survival (HR 1.755 [95% CI 1.031–2.988], p=0.038). Its prognostic value for overall survival was more predominant in patients with clear cell renal cell carcinoma (p <0.001) or patients in the intermediate risk group of Heng risk criteria (p <0.001), while its predictive value for progression-free survival was more predominant in patients treated with sorafenib (p <0.001). SETD2 could also be combined with the Heng risk model for better overall survival prediction.

Conclusions

SETD2 is a potential prognostic biomarker for overall survival and progression-free survival prediction in patients with metastatic renal cell carcinoma receiving targeted therapy. However, it remains to be seen whether this is generalizable to other ethnicities and prospective external validation is required.