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 Palli & 14 others Sabina 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

Fingerprint

Kidney Neoplasms
Early Detection of Cancer
Case-Control Studies
Renal Cell Carcinoma
Kidney
Wounds and Injuries
Survival
Incidence
Confidence Intervals
Plasma Cells
Blood Donors
ROC Curve
Body Mass Index
Cohort Studies
Research Design
Logistic Models
Smoking
Parturition
Prospective Studies

Cite this

Scelo, G., Muller, D. C., Riboli, E., Johansson, M., Cross, A. J., Vineis, P., ... 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

KIM-1 as a Blood-Based Marker for Early Detection of Kidney Cancer : A Prospective Nested Case-Control Study. / Scelo, Ghislaine; Muller, David C; Riboli, Elio; Johansson, Mattias; Cross, Amanda J; Vineis, Paolo; Tsilidis, Konstantinos K; Brennan, Paul; Boeing, Heiner; Peeters, Petra H M; Vermeulen, Roel C H; Overvad, Kim; Bueno-de-Mesquita, H Bas; Severi, Gianluca; Perduca, Vittorio; Kvaskoff, Marina; Trichopoulou, Antonia; La Vecchia, Carlo; Karakatsani, Anna; Palli, Domenico; Sieri, Sabina; Panico, Salvatore; Weiderpass, Elisabete; Sandanger, Torkjel M; Nøst, Therese H; Agudo, Antonio; Quirós, J Ramón; Rodríguez-Barranco, Miguel; Chirlaque, Maria-Dolores; Key, Timothy J; Khanna, Prateek; Bonventre, Joseph V; Sabbisetti, Venkata S; Bhatt, Rupal S.

In: Clinical Cancer Research, Vol. 24, No. 22, 15.11.2018, p. 5594-5601.

Research output: Contribution to journalArticle

Scelo, G, Muller, DC, Riboli, E, Johansson, M, Cross, AJ, Vineis, P, Tsilidis, KK, Brennan, P, Boeing, H, Peeters, PHM, Vermeulen, RCH, Overvad, K, Bueno-de-Mesquita, HB, Severi, G, Perduca, V, Kvaskoff, M, Trichopoulou, A, La Vecchia, C, Karakatsani, A, Palli, D, Sieri, S, Panico, S, Weiderpass, E, Sandanger, TM, Nøst, TH, Agudo, A, Quirós, JR, Rodríguez-Barranco, M, Chirlaque, M-D, Key, TJ, Khanna, P, Bonventre, JV, Sabbisetti, VS & Bhatt, RS 2018, 'KIM-1 as a Blood-Based Marker for Early Detection of Kidney Cancer: A Prospective Nested Case-Control Study', Clinical Cancer Research, vol. 24, no. 22, pp. 5594-5601. https://doi.org/10.1158/1078-0432.CCR-18-1496
Scelo, Ghislaine ; Muller, David C ; Riboli, Elio ; Johansson, Mattias ; Cross, Amanda J ; Vineis, Paolo ; Tsilidis, Konstantinos K ; Brennan, Paul ; Boeing, Heiner ; Peeters, Petra H M ; Vermeulen, Roel C H ; Overvad, Kim ; Bueno-de-Mesquita, H Bas ; Severi, Gianluca ; Perduca, Vittorio ; Kvaskoff, Marina ; Trichopoulou, Antonia ; La Vecchia, Carlo ; Karakatsani, Anna ; Palli, Domenico ; Sieri, Sabina ; Panico, Salvatore ; Weiderpass, Elisabete ; Sandanger, Torkjel M ; Nøst, Therese H ; Agudo, Antonio ; Quirós, J Ramón ; Rodríguez-Barranco, Miguel ; Chirlaque, Maria-Dolores ; Key, Timothy J ; Khanna, Prateek ; Bonventre, Joseph V ; Sabbisetti, Venkata S ; Bhatt, Rupal S. / KIM-1 as a Blood-Based Marker for Early Detection of Kidney Cancer : A Prospective Nested Case-Control Study. In: Clinical Cancer Research. 2018 ; Vol. 24, No. 22. pp. 5594-5601.
@article{b3c608c4f50a4cc8917d94d3055e339e,
title = "KIM-1 as a Blood-Based Marker for Early Detection of Kidney Cancer: A Prospective Nested Case-Control Study",
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. {\circledC}2018 AACR.",
author = "Ghislaine Scelo and Muller, {David C} and Elio Riboli and Mattias Johansson and Cross, {Amanda J} and Paolo Vineis and Tsilidis, {Konstantinos K} and Paul Brennan and Heiner Boeing and Peeters, {Petra H M} and Vermeulen, {Roel C H} and Kim Overvad and Bueno-de-Mesquita, {H Bas} and Gianluca Severi and Vittorio Perduca and Marina Kvaskoff and Antonia Trichopoulou and {La Vecchia}, Carlo and Anna Karakatsani and Domenico Palli and Sabina Sieri and Salvatore Panico and Elisabete Weiderpass and Sandanger, {Torkjel M} and N{\o}st, {Therese H} and Antonio Agudo and Quir{\'o}s, {J Ram{\'o}n} and Miguel Rodr{\'i}guez-Barranco and Maria-Dolores Chirlaque and Key, {Timothy J} and Prateek Khanna and Bonventre, {Joseph V} and Sabbisetti, {Venkata S} and Bhatt, {Rupal S}",
note = "{\circledC}2018 American Association for Cancer Research.",
year = "2018",
month = "11",
day = "15",
doi = "10.1158/1078-0432.CCR-18-1496",
language = "English",
volume = "24",
pages = "5594--5601",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "22",

}

TY - JOUR

T1 - KIM-1 as a Blood-Based Marker for Early Detection of Kidney Cancer

T2 - A Prospective Nested Case-Control Study

AU - Scelo, Ghislaine

AU - Muller, David C

AU - Riboli, Elio

AU - Johansson, Mattias

AU - Cross, Amanda J

AU - Vineis, Paolo

AU - Tsilidis, Konstantinos K

AU - Brennan, Paul

AU - Boeing, Heiner

AU - Peeters, Petra H M

AU - Vermeulen, Roel C H

AU - Overvad, Kim

AU - Bueno-de-Mesquita, H Bas

AU - Severi, Gianluca

AU - Perduca, Vittorio

AU - Kvaskoff, Marina

AU - Trichopoulou, Antonia

AU - La Vecchia, Carlo

AU - Karakatsani, Anna

AU - Palli, Domenico

AU - Sieri, Sabina

AU - Panico, Salvatore

AU - Weiderpass, Elisabete

AU - Sandanger, Torkjel M

AU - Nøst, Therese H

AU - Agudo, Antonio

AU - Quirós, J Ramón

AU - Rodríguez-Barranco, Miguel

AU - Chirlaque, Maria-Dolores

AU - Key, Timothy J

AU - Khanna, Prateek

AU - Bonventre, Joseph V

AU - Sabbisetti, Venkata S

AU - Bhatt, Rupal S

N1 - ©2018 American Association for Cancer Research.

PY - 2018/11/15

Y1 - 2018/11/15

N2 - 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.

AB - 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.

U2 - 10.1158/1078-0432.CCR-18-1496

DO - 10.1158/1078-0432.CCR-18-1496

M3 - Article

VL - 24

SP - 5594

EP - 5601

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 22

ER -