Volume 67, Issue 1, Pages (January 2015)

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Volume 67, Issue 1, Pages 17-20 (January 2015) A Multigene Assay Identifying Distinct Prognostic Subtypes of Clear Cell Renal Cell Carcinoma with Differential Response to Tyrosine Kinase Inhibition Yukti Choudhury, Xiaona Wei, Ying-Hsia Chu, Lay Guat Ng, Hui Shan Tan, Valerie Koh, Aye Aye Thike, Eileen Poon, Quan Sing Ng, Chee Keong Toh, Ravindran Kanesvaran, Puay Hoon Tan, Min-Han Tan European Urology Volume 67, Issue 1, Pages 17-20 (January 2015) DOI: 10.1016/j.eururo.2014.06.041 Copyright © 2014 European Association of Urology Terms and Conditions

Fig. 1 Hierarchical clustering analysis of 55 clear cell renal cell carcinomas (ccRCC) based on DASL expression data identifies two prognostic subtypes. (A) Cluster dendrogram of 55 ccRCC samples grouped by expression of 3740 genes measured by DASL analysis. Two main groups are formed (n1=43 and n2=12), denoted by blue branches and orange branches in the dendrogram. (B) Kaplan-Meier curves of cancer-specific survival (CSS) for two prognostic subtypes generated by hierarchical clustering. Survival in the good-prognosis subtype is significantly better than in the poor-prognosis group (log-rank test p=0.0185). CI=confidence interval; HR=hazard ratio; NR=not reached. European Urology 2015 67, 17-20DOI: (10.1016/j.eururo.2014.06.041) Copyright © 2014 European Association of Urology Terms and Conditions

Fig. 2 Validation of an eight-gene, prognosis subtype-classification algorithm for clear cell renal cell carcinomas (ccRCC), including utility in predicting survival in patients with metastatic ccRCC who received tyrosine kinase inhibitor (TKI) therapy. (A–C) Survival analysis by Kaplan-Meier method for ccRCC patients classified into good- and poor-prognosis subtypes based on expression of eight genes. A difference is observed in cancer-specific survival (CSS) between two prognosis subtypes. (D–E) Survival analysis for TKI-receiving patients similarly classified into prognosis groups. The p values are derived from log-rank tests. (A) Prognostic subtype assignment for Singapore General Hospital (SGH)-224 validation cohort (n=224) based on quantitative polymerase chain reaction gene expression measurement in formalin-fixed paraffin-embedded tumors. (B) Prognostic subtype assignment for the Cancer Genome Atlas (TCGA)-419 validation cohort (n=419) by classification algorithm applied to RNA-sequencing expression data. It should be noted that the TCGA dataset is enriched in patients with higher-grade disease with an overall poor survival outlook, with only five samples classified as histologic grade 1 tumors. (C) Prognostic subtype assignment for Van Andel Research Institute (VARI)-174 validation cohort based on Affymetrix microarray expression data (Affymetrix, Santa Clara, CA, USA). (D) CSS of patients with metastatic ccRCC receiving TKI therapy in first-, second-, and third-line settings. (E) CSS of patients with metastatic ccRCC receiving TKI therapy in the first-line setting. CI=confidence interval; HR=hazard ratio; NR=median survival time not reached. European Urology 2015 67, 17-20DOI: (10.1016/j.eururo.2014.06.041) Copyright © 2014 European Association of Urology Terms and Conditions