PTRF independently predicts progression and survival in multiracial upper tract urothelial carcinoma following radical nephroureterectomy

Hsin Chih Yeh, Vitaly Margulis, Nirmish Singla, Elizabeth Hernandez, Vandana Panwar, Solomon L. Woldu, Jose A. Karam, Christopher G. Wood, Alon Z. Weizer, Jay D. Raman, Mesut Remzi, Nathalie Rioux-Leclercq, Andrea Haitel, Marco Roscigno, Christian Bolenz, Karim Bensalah, Ching Chia Li, Hung Lung Ke, Wei Ming Li, Hsiang Ying LeeLeonid M. Rapoport, Yair Lotan, Payal Kapur, Shahrokh F. Shariat, Jer Tsong Hsieh, Wen Jeng Wu

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: Polymerase I and transcript release factor (PTRF) has been implicated in cancer biology but its role in upper tract urothelial carcinoma (UTUC) is unknown. From a pilot transcriptome, we identified PTRF was significantly upregulated in high stage UTUC. Bladder cancer transcriptome from The Cancer Genome Atlas (TCGA) supported our finding and high PTRF level also predicted poor survival. We, therefore, investigated the correlation of PTRF with patients’ clinicopathologic characteristics and outcomes in a multiracial UTUC cohort. Materials and methods: By immunohistochemical staining, PTRF expression was determined using H-score. PTRF expression of 575 UTUCs from 8 institutions, including 118 Asians and 457 Caucasians, was compared with various clinicopathologic parameters. Human urothelial cancer cell lines were used to evaluate the level of PTRF protein and mRNA expression, and PTRF transcript level was assessed in fresh samples from 12 cases of the cohort. The impact of PTRF expression on disease progression, cancer-specific death and overall mortality was also examined. Results: High PTRF expression was significantly associated with multifocality (P = 0.023), high pathologic tumor stage (P < 0.00001), nonurothelial differentiation (P = 0.035), lymphovascular invasion (P = 0.003) and lymph node metastasis (P = 0.031). PTRF mRNA expression was also markedly increased in advanced stage UTUC (P = 0.0003). High PTRF expressing patients had consistently worse outcomes than patients with low PTRF expression regardless of demographic variation (all P < 0.005). In multivariate analysis, high PTRF expression was an independent predictor for progression-free survival (hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.07–2.69, P = 0.025), cancer-specific survival (HR 2.09, 95% CI 1.28–3.42, P = 0.003), and overall survival (HR 2.04, 95% CI 1.33–3.14, P = 0.001). Conclusions: Results indicate that PTRF is a predictive biomarker for progression and survival and an independent prognosticator of UTUC. Elevated PTRF could probably propel clinically aggressive disease and serve as a potential therapeutic target for UTUC.

Original languageEnglish (US)
Pages (from-to)496-505
Number of pages10
JournalUrologic Oncology: Seminars and Original Investigations
Volume38
Issue number5
DOIs
StatePublished - May 2020

Keywords

  • Immunohistochemical staining
  • Polymerase I and transcript release factor
  • Prognosis
  • Progression
  • Upper tract urothelial carcinoma
  • Urothelial carcinoma of bladder

ASJC Scopus subject areas

  • Oncology
  • Urology

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