BACKGROUND: Prognostic value of arm somatic copy number alterations (SCNAs) in clear cell renal cell carcinoma (ccRCC) have not been systematically evaluated in a large cohort. Its association with tumor microenvironment remained unknown. METHODS: We retrospectively correlated arm SCNAs with OS and recurrence free survival (RFS) in a cohort of 524 ccRCC patients. The prognostic landscape of arm SCNA was depicted by bubble heatmap. Associations between arm SCNAs and tumor microenvironment were evaluated by CIBERSORT and Gene Set Enrichment Analysis (GSEA). RESULTS: We found that amplifications of 1p, 3p and loss of 4p, 4q, 5p, 5q, 11p, 11q, 11q, 13q, 19p were independent adverse risk factor for OS, while amplification of 1q and deletions of 4p, 4q, 9p, 9q associated with worse RFS. Loss of 4q were independent adverse risk factor for OS (P=0.012, HR =1.614) and RFS (P=0.001, HR =2.005). It could identify a subset of early stage ccRCC patients with high risk of death and recurrence. CXCL9, CXCL10, CXCL11 mRNA level and CD8+ T cell infiltration were downregulated in ccRCC with 4q deletion. Patients with high arm SCNA level had shorter OS (P=0.005) and RFS (P=0.001). Markers, immune cells and pathways referring to immune suppression were elevated in tumors with high arm SCNA level. CONCLUSIONS: In conclusion, loss of 4q was an independent adverse risk factor for OS and RFS in ccRCC patients and contributed to cytotoxic cell exclusion via downregulation of CXCL9, CXCL10 and CXCL11. Patients with higher arm SCNAs had worse survival and a more immunosuppressive tumor microenvironment. 2019 Annals of Translational Medicine. All rights reserved.
BACKGROUND: Prognostic value of arm somatic copy number alterations (SCNAs) in clear cell renal cell carcinoma (ccRCC) have not been systematically evaluated in a large cohort. Its association with tumor microenvironment remained unknown. METHODS: We retrospectively correlated arm SCNAs with OS and recurrence free survival (RFS) in a cohort of 524 ccRCC patients. The prognostic landscape of arm SCNA was depicted by bubble heatmap. Associations between arm SCNAs and tumor microenvironment were evaluated by CIBERSORT and Gene Set Enrichment Analysis (GSEA). RESULTS: We found that amplifications of 1p, 3p and loss of 4p, 4q, 5p, 5q, 11p, 11q, 11q, 13q, 19p were independent adverse risk factor for OS, while amplification of 1q and deletions of 4p, 4q, 9p, 9q associated with worse RFS. Loss of 4q were independent adverse risk factor for OS (P=0.012, HR =1.614) and RFS (P=0.001, HR =2.005). It could identify a subset of early stage ccRCC patients with high risk of death and recurrence. CXCL9, CXCL10, CXCL11 mRNA level and CD8+ T cell infiltration were downregulated in ccRCC with 4q deletion. Patients with high arm SCNA level had shorter OS (P=0.005) and RFS (P=0.001). Markers, immune cells and pathways referring to immune suppression were elevated in tumors with high arm SCNA level. CONCLUSIONS: In conclusion, loss of 4q was an independent adverse risk factor for OS and RFS in ccRCC patients and contributed to cytotoxic cell exclusion via downregulation of CXCL9, CXCL10 and CXCL11. Patients with higher arm SCNAs had worse survival and a more immunosuppressive tumor microenvironment. 2019 Annals of Translational Medicine. All rights reserved.
Authors: Andrew J Gentles; Aaron M Newman; Chih Long Liu; Scott V Bratman; Weiguo Feng; Dongkyoon Kim; Viswam S Nair; Yue Xu; Amanda Khuong; Chuong D Hoang; Maximilian Diehn; Robert B West; Sylvia K Plevritis; Ash A Alizadeh Journal: Nat Med Date: 2015-07-20 Impact factor: 53.440
Authors: Timothy Ito; Jianming Pei; Essel Dulaimi; Craig Menges; Philip H Abbosh; Marc C Smaldone; David Y T Chen; Richard E Greenberg; Alexander Kutikov; Rosalia Viterbo; Robert G Uzzo; Joseph R Testa Journal: J Urol Date: 2015-11-18 Impact factor: 7.450
Authors: Aaron M Newman; Chih Long Liu; Michael R Green; Andrew J Gentles; Weiguo Feng; Yue Xu; Chuong D Hoang; Maximilian Diehn; Ash A Alizadeh Journal: Nat Methods Date: 2015-03-30 Impact factor: 28.547