Prognostic impact of insulin-like growth factor-I and its binding proteins, insulin-like growth factor-I binding protein-2 and -3, on adverse histopathological features and survival outcomes after radical cystectomy

Reza Sari Motlagh, Victor M. Schuettfort, Keiichiro Mori, Satoshi Katayama, Pawel Rajwa, Abdulmajeed Aydh, Nico C. Grossmann, Ekaterina Laukhtina, Benjamin Pradere, Hadi Mostafai, Fahad Quhal, Mohammad Abufaraj, Richard Lee, Pierre I. Karakiewicz, Yair Lotan, Eva Comprate, Marco Moschini, Paolo Gontero, Shahrokh F. Shariat

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Objectives: Insulin-like growth factor-I and its binding proteins are involved in cancer development, progression, and metastasis. In urothelial carcinoma, the impact of this pathway is still poorly investigated. The present large cohort study aimed to evaluate the association of preoperative circulating levels of insulin-like growth factor-I, insulin-like growth factor-I binding protein-2 and -3 on outcomes after radical cystectomy. Methods: A retrospective cohort study of the plasma specimens from 1036 consecutive urothelial carcinoma patients who were treated with radical cystectomy. The primary and secondary outcomes were adverse histopathological features and survival outcomes. Binominal logistic regression and multivariable Cox regression analyses were performed to assess the association of plasma levels of insulin-like growth factor-I, insulin-like growth factor-I binding protein-2 and -3 with outcomes. Results: On multivariable analysis adjusting for the effects of preoperative variables, lower insulin-like growth factor-I binding protein-2 levels were associated with an increased risk of lymph node metastasis and (any non-organ confined disease) any non-organ confined disease. Insulin-like growth factor-I binding protein-3 levels were also inversely independently associated with lymph node metastasis. Receiver operating characteristic curve analysis showed that the addition of insulin-like growth factor-I binding proteins biomarkers to a reference model significantly improved the discriminating ability for the prediction of lymph node metastasis (+10.0%, P < 0.001). On multivariable Cox regression models, lower levels of both insulin-like growth factor-I binding protein-2 and -3 plasma levels were associated with recurrence-free survival, cancer-specific survival, and overall survival. insulin-like growth factor-I binding protein-2 and -3 levels and improved the discrimination of a standard reference model for the prediction of recurrence-free survival, cancer-specific survival, and overall survival (+4.9%, 4.9%, 2.3%, respectively). Conclusions: Preoperative insulin-like growth factor-I binding protein-2 and -3 are significantly associated with features of biologically and clinically aggressive urothelial carcinoma. These biomarkers improved prognostic urothelial carcinoma models.

Original languageEnglish
Pages (from-to)676-683
Number of pages8
JournalInternational Journal of Urology
Volume29
Issue number7
DOIs
Publication statusPublished - Jul 2022

Keywords

  • binding proteins
  • bladder cancer
  • IGF-I
  • insulin-like growth factor
  • radical cystectomy
  • urothelial carcinoma

ASJC Scopus subject areas

  • Urology

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