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



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.



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.



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.
Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
Jiajun
J
Wang
Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
Li
L
Liu
Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
Yang
Y
Qu
Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
Wei
W
Xi
Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
Yu
Y
Xia
Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
Qi
Q
Bai
Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
Ying
Y
Xiong
Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
Qilai
Q
Long
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China. Electronic address: jjxufdu@fudan.edu.cn.
Jiejie
J
Xu
Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: guo.jianming@zs-hospital.sh.cn.
Jianming
J
Guo
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics* / Q000556:secondary; D018572:Disease-Free Survival; D015972:Gene Expression Regulation, Neoplastic; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011758:Pyrroles / Q000627:therapeutic use*; D012189:Retrospective Studies; D000077157:Sorafenib; D000077210:Sunitinib; D055815:Young Adult
D000970:Antineoplastic Agents; D007211:Indoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D009536:Niacinamide; D000077157:Sorafenib; D011495:Histone-Lysine N-Methyltransferase; C521636:SETD2 protein, human; D011505:Protein-Tyrosine Kinases; D000077210:Sunitinib
biomarkers; carcinoma; disease-free survival; neoplasm metastasis; renal cell; survival