Frontiers in Cell and Developmental Biology (Aug 2021)
Copy Number Signatures and Clinical Outcomes in Upper Tract Urothelial Carcinoma
- Bao Guan,
- Bao Guan,
- Bao Guan,
- Bao Guan,
- Yuan Liang,
- Huan Lu,
- Huan Lu,
- Zhengzheng Xu,
- Zhengzheng Xu,
- Yue Shi,
- Juan Li,
- Juan Li,
- Wenwen Kong,
- Wenwen Kong,
- Chuanyu Tian,
- Chuanyu Tian,
- Yezhen Tan,
- Yezhen Tan,
- Yanqing Gong,
- Yanqing Gong,
- Yanqing Gong,
- Jin Liu,
- Dong Fang,
- Dong Fang,
- Qi Shen,
- Qi Shen,
- Qi Shen,
- Shiming He,
- Shiming He,
- Shiming He,
- Muhammad Shakeel,
- Muhammad Shakeel,
- Zhongyuan Zhang,
- Zhongyuan Zhang,
- Zhongyuan Zhang,
- Qun He,
- Qun He,
- Qun He,
- Xuesong Li,
- Xuesong Li,
- Xuesong Li,
- Weimin Ci,
- Weimin Ci,
- Weimin Ci,
- Liqun Zhou,
- Liqun Zhou,
- Liqun Zhou
Affiliations
- Bao Guan
- Department of Urology, Peking University First Hospital, Beijing, China
- Bao Guan
- Key Laboratory of Genomics and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
- Bao Guan
- Institute of Urology, Peking University, Beijing, China
- Bao Guan
- Beijing Key Laboratory of Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, National Urological Cancer Center, Beijing, China
- Yuan Liang
- Key Laboratory of Genomics and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
- Huan Lu
- Key Laboratory of Genomics and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
- Huan Lu
- University of Chinese Academy of Sciences, Beijing, China
- Zhengzheng Xu
- Key Laboratory of Genomics and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
- Zhengzheng Xu
- University of Chinese Academy of Sciences, Beijing, China
- Yue Shi
- Key Laboratory of Genomics and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
- Juan Li
- Key Laboratory of Genomics and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
- Juan Li
- University of Chinese Academy of Sciences, Beijing, China
- Wenwen Kong
- Key Laboratory of Genomics and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
- Wenwen Kong
- University of Chinese Academy of Sciences, Beijing, China
- Chuanyu Tian
- Key Laboratory of Genomics and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
- Chuanyu Tian
- University of Chinese Academy of Sciences, Beijing, China
- Yezhen Tan
- Key Laboratory of Genomics and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
- Yezhen Tan
- University of Chinese Academy of Sciences, Beijing, China
- Yanqing Gong
- Department of Urology, Peking University First Hospital, Beijing, China
- Yanqing Gong
- Institute of Urology, Peking University, Beijing, China
- Yanqing Gong
- Beijing Key Laboratory of Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, National Urological Cancer Center, Beijing, China
- Jin Liu
- Department of Urology, The Third Hospital of Hebei Medical University, Shijiazhuang, China
- Dong Fang
- Department of Urology, Peking University First Hospital, Beijing, China
- Dong Fang
- Beijing Key Laboratory of Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, National Urological Cancer Center, Beijing, China
- Qi Shen
- Department of Urology, Peking University First Hospital, Beijing, China
- Qi Shen
- Institute of Urology, Peking University, Beijing, China
- Qi Shen
- Beijing Key Laboratory of Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, National Urological Cancer Center, Beijing, China
- Shiming He
- Department of Urology, Peking University First Hospital, Beijing, China
- Shiming He
- Institute of Urology, Peking University, Beijing, China
- Shiming He
- Beijing Key Laboratory of Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, National Urological Cancer Center, Beijing, China
- Muhammad Shakeel
- Key Laboratory of Genomics and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
- Muhammad Shakeel
- Jamil-ur-Rahman Center for Genome Research, PCMD, ICCBS, University of Karachi, Karachi, Pakistan
- Zhongyuan Zhang
- Department of Urology, Peking University First Hospital, Beijing, China
- Zhongyuan Zhang
- Institute of Urology, Peking University, Beijing, China
- Zhongyuan Zhang
- Beijing Key Laboratory of Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, National Urological Cancer Center, Beijing, China
- Qun He
- Department of Urology, Peking University First Hospital, Beijing, China
- Qun He
- Institute of Urology, Peking University, Beijing, China
- Qun He
- Beijing Key Laboratory of Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, National Urological Cancer Center, Beijing, China
- Xuesong Li
- Department of Urology, Peking University First Hospital, Beijing, China
- Xuesong Li
- Institute of Urology, Peking University, Beijing, China
- Xuesong Li
- Beijing Key Laboratory of Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, National Urological Cancer Center, Beijing, China
- Weimin Ci
- Key Laboratory of Genomics and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
- Weimin Ci
- University of Chinese Academy of Sciences, Beijing, China
- Weimin Ci
- Institute of Stem cell and Regeneration, Chinese Academy of Sciences, Beijing, China
- Liqun Zhou
- Department of Urology, Peking University First Hospital, Beijing, China
- Liqun Zhou
- Institute of Urology, Peking University, Beijing, China
- Liqun Zhou
- Beijing Key Laboratory of Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, National Urological Cancer Center, Beijing, China
- DOI
- https://doi.org/10.3389/fcell.2021.713499
- Journal volume & issue
-
Vol. 9
Abstract
Tumor staging of upper tract urothelial carcinomas (UTUCs) is relatively difficult to assert accurately before surgery. Here, we used copy number (CN) signatures as a tool to explore their clinical significance of molecular stratification in UTUC. CN signatures were extracted by non-negative matrix factorization from the whole-genome sequencing (WGS) data of 90 Chinese UTUC primary tumor samples. A validation UTUC cohort (n = 56) and a cohort from urinary cell-free DNA (cfDNA) of urothelial cancer patients (n = 94) and matched primary tumors were also examined. Survival analyses were measured using the Kaplan–Meier, and Cox regression was used for multivariate analysis. Here, we identified six CN signatures (Sig1–6). Patients with a high contribution of Sig6 (Sig6high) were associated with higher microsatellite instability level and papillary architecture and had a favorable outcome. Patients with a low weighted genome integrity index were associated with positive lymph node and showed the worst outcome. Sig6high was identified to be an independently prognostic factor. The predictive significance of CN signature was identified by a validation UTUC cohort. CN signatures retained great concordance between primary tumor and urinary cfDNA. In conclusion, our results reveal that CN signature assessment for risk stratification is feasible and provides a basis for clinical studies that evaluate therapeutic interventions and prognosis.
Keywords
- upper tract urothelial carcinoma
- whole-genome sequencing
- copy number signature
- prognosis
- cell-free DNA