Plasma proteomic profiling discovers molecular features associated with upper tract urothelial carcinoma

Upper tract urothelial carcinoma (UTUC) is often diagnosed late and exhibits poor prognosis. Limited data are available on potential non-invasive biomarkers for disease monitoring. Here, we investigate the proteomic profile of plasma in 362 UTUC patients and 239 healthy controls. We present an integrated tissue-plasma proteomic approach to infer the signature proteins for identifying patients with muscle-invasive UTUC. We discover a protein panel that reflects lymph node metastasis, which is of interest in identifying UTUC patients with high risk and poor prognosis. We also identify a ten-protein classifier and establish a progression clock predicting progression-free survival of UTUC patients. Finally, we further validate the signature proteins by parallel reaction monitoring assay in an independent cohort. Collectively, this study portrays the plasma proteomic landscape of a UTUC cohort and provides a valuable resource for further biological and diagnostic research in UTUC. • Proteomic profiles of plasma in UTUC patients with a 5-year follow-up • Discovery of the plasma signature proteins associated with UTUC • Construction of predictive model distinguishing between MI-UTUCs and NMI-UTUCs • Identification of progression clock predicting progression-free survival of UTUC patients Upper tract urothelial cancer (UTUC) is a relatively uncommon but more aggressive form of urothelial cancer. It is often diagnosed late and has poor prognosis. Qu et al. portray a plasma proteomic landscape of UTUC and provide predictive models that could potentially improve the diagnosis and management of UTUC.