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

DOI
https://doi.org/10.3389/fcell.2021.713499
Journal volume & issue
Vol. 9

Abstract

Read online

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