KIM-1 as a Blood-Based Marker for Early Detection of Kidney Cancer: A Prospective Nested Case-Control Study

Ghislaine Scelo, David C Muller, Elio Riboli, Mattias Johansson, Amanda J Cross, Paolo Vineis, Konstantinos K Tsilidis, Paul Brennan, Heiner Boeing, Petra H M Peeters, Roel C H Vermeulen, Kim Overvad, H Bas Bueno-de-Mesquita, Gianluca Severi, Vittorio Perduca, Marina Kvaskoff, Antonia Trichopoulou, Carlo La Vecchia, Anna Karakatsani, Domenico PalliSabina Sieri, Salvatore Panico, Elisabete Weiderpass, Torkjel M Sandanger, Therese H Nøst, Antonio Agudo, J Ramón Quirós, Miguel Rodríguez-Barranco, Maria-Dolores Chirlaque, Timothy J Key, Prateek Khanna, Joseph V Bonventre, Venkata S Sabbisetti, Rupal S Bhatt

Research output: Contribution to journalArticle

Abstract

Purpose: Renal cell carcinoma (RCC) has the potential for cure with surgery when diagnosed at an early stage. Kidney injury molecule-1 (KIM-1) has been shown to be elevated in the plasma of RCC patients. We aimed to test whether plasma KIM-1 could represent a means of detecting RCC prior to clinical diagnosis.Experimental Design: KIM-1 concentrations were measured in prediagnostic plasma from 190 RCC cases and 190 controls nested within a population-based prospective cohort study. Cases had entered the cohort up to 5 years before diagnosis, and controls were matched on cases for date of birth, date at blood donation, sex, and country. We applied conditional logistic regression and flexible parametric survival models to evaluate the association between plasma KIM-1 concentrations and RCC risk and survival.Results: The incidence rate ratio (IRR) of RCC for a doubling in KIM-1 concentration was 1.71 [95% confidence interval (CI), 1.44-2.03, P = 4.1 × 10-23], corresponding to an IRR of 63.3 (95% CI, 16.2-246.9) comparing the 80th to the 20th percentiles of the KIM-1 distribution in this sample. Compared with a risk model including known risk factors of RCC (age, sex, country, body mass index, and tobacco smoking status), a risk model additionally including KIM-1 substantially improved discrimination between cases and controls (area under the receiver-operating characteristic curve of 0.8 compared with 0.7). High plasma KIM-1 concentrations were also associated with poorer survival (P = 0.0053).Conclusions: Plasma KIM-1 concentrations could predict RCC incidence up to 5 years prior to diagnosis and were associated with poorer survival. Clin Cancer Res; 24(22); 5594-601. ©2018 AACR.

Original languageEnglish
Pages (from-to)5594-5601
Number of pages8
JournalClinical Cancer Research
Volume24
Issue number22
DOIs
Publication statusPublished - Nov 15 2018

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    Scelo, G., Muller, D. C., Riboli, E., Johansson, M., Cross, A. J., Vineis, P., Tsilidis, K. K., Brennan, P., Boeing, H., Peeters, P. H. M., Vermeulen, R. C. H., Overvad, K., Bueno-de-Mesquita, H. B., Severi, G., Perduca, V., Kvaskoff, M., Trichopoulou, A., La Vecchia, C., Karakatsani, A., ... Bhatt, R. S. (2018). KIM-1 as a Blood-Based Marker for Early Detection of Kidney Cancer: A Prospective Nested Case-Control Study. Clinical Cancer Research, 24(22), 5594-5601. https://doi.org/10.1158/1078-0432.CCR-18-1496