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

TY - JOUR

T1 - 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

AU - Sari Motlagh, Reza

AU - Schuettfort, Victor M

AU - Mori, Keiichiro

AU - Katayama, Satoshi

AU - Rajwa, Pawel

AU - Aydh, Abdulmajeed

AU - Grossmann, Nico C

AU - Laukhtina, Ekaterina

AU - Pradere, Benjamin

AU - Mostafai, Hadi

AU - Quhal, Fahad

AU - Abufaraj, Mohammad

AU - Lee, Richard

AU - Karakiewicz, Pierre I

AU - Lotan, Yair

AU - Comprate, Eva

AU - Moschini, Marco

AU - Gontero, Paolo

AU - Shariat, Shahrokh F

N1 - © 2022 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Urological Association.

PY - 2022/7

Y1 - 2022/7

N2 - 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.

AB - 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.

KW - Biomarkers

KW - Carcinoma, Transitional Cell/pathology

KW - Carrier Proteins

KW - Cohort Studies

KW - Cystectomy

KW - Humans

KW - Insulin-Like Growth Factor Binding Protein 2/genetics

KW - Insulin-Like Growth Factor Binding Protein 3/genetics

KW - Insulin-Like Growth Factor I/genetics

KW - Lymphatic Metastasis

KW - Neoplasm Staging

KW - Prognosis

KW - Retrospective Studies

KW - Urinary Bladder Neoplasms/pathology

U2 - 10.1111/iju.14869

DO - 10.1111/iju.14869

M3 - SCORING: Journal article

C2 - 35368130

VL - 29

SP - 676

EP - 683

JO - INT J UROL

JF - INT J UROL

SN - 0919-8172

IS - 7

ER -