Design and methodological considerations for biomarker discovery and validation in the Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Program

Hilary A. Robbins; Karine Alcala; Elham Khodayari Moez; Florence Guida; Sera Thomas; Hana Zahed; Matthew T. Warkentin; Karl Smith-Byrne; Yonathan Brhane; David Muller; Xiaoshuang Feng; Demetrius Albanes; Melinda C. Aldrich; Alan A. Arslan; Julie Bassett; Christine D. Berg; Qiuyin Cai; Chu Chen; Michael P.A. Davies; Brenda Diergaarde; John K. Field; Neal D. Freedman; Wen Yi Huang; Mikael Johansson; Michael Jones; Woon Puay Koh; Stephen Lam; Qing Lan; Arnulf Langhammer; Linda M. Liao; Geoffrey Liu; Reza Malekzadeh; Roger L. Milne; Luis M. Montuenga; Thomas Rohan; Howard D. Sesso; Gianluca Severi; Mahdi Sheikh; Rashmi Sinha; Xiao Ou Shu; Victoria L. Stevens; Martin C. Tammemägi; Lesley F. Tinker; Kala Visvanathan; Ying Wang; Renwei Wang; Stephanie J. Weinstein; Emily White; David Wilson; Jian Min Yuan; Xuehong Zhang; Wei Zheng; Christopher I. Amos; Paul Brennan; Mattias Johansson; Rayjean J. Hung

doi:10.1016/j.annepidem.2022.10.014

Design and methodological considerations for biomarker discovery and validation in the Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Program

Hilary A. Robbins, Karine Alcala, Elham Khodayari Moez, Florence Guida, Sera Thomas, Hana Zahed, Matthew T. Warkentin, Karl Smith-Byrne, Yonathan Brhane, David Muller, Xiaoshuang Feng, Demetrius Albanes, Melinda C. Aldrich, Alan A. Arslan, Julie Bassett, Christine D. Berg, Qiuyin Cai, Chu Chen, Michael P.A. Davies, Brenda DiergaardeJohn K. Field, Neal D. Freedman, Wen Yi Huang, Mikael Johansson, Michael Jones, Woon Puay Koh, Stephen Lam, Qing Lan, Arnulf Langhammer, Linda M. Liao, Geoffrey Liu, Reza Malekzadeh, Roger L. Milne, Luis M. Montuenga, Thomas Rohan, Howard D. Sesso, Gianluca Severi, Mahdi Sheikh, Rashmi Sinha, Xiao Ou Shu, Victoria L. Stevens, Martin C. Tammemägi, Lesley F. Tinker, Kala Visvanathan, Ying Wang, Renwei Wang, Stephanie J. Weinstein, Emily White, David Wilson, Jian Min Yuan, Xuehong Zhang, Wei Zheng, Christopher I. Amos, Paul Brennan, Mattias Johansson, Rayjean J. Hung

Epidemiology & Population Health

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

The Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) program is an NCI-funded initiative with an objective to develop tools to optimize low-dose CT (LDCT) lung cancer screening. Here, we describe the rationale and design for the Risk Biomarker and Nodule Malignancy projects within INTEGRAL. The overarching goal of these projects is to systematically investigate circulating protein markers to include on a panel for use (i) pre-LDCT, to identify people likely to benefit from screening, and (ii) post-LDCT, to differentiate benign versus malignant nodules. To identify informative proteins, the Risk Biomarker project measured 1161 proteins in a nested-case control study within 2 prospective cohorts (n = 252 lung cancer cases and 252 controls) and replicated associations for a subset of proteins in 4 cohorts (n = 479 cases and 479 controls). Eligible participants had a current or former history of smoking and cases were diagnosed up to 3 years following blood draw. The Nodule Malignancy project measured 1078 proteins among participants with a heavy smoking history within four LDCT screening studies (n = 425 cases diagnosed up to 5 years following blood draw, 430 benign-nodule controls, and 398 nodule-free controls). The INTEGRAL panel will enable absolute quantification of 21 proteins. We will evaluate its performance in the Risk Biomarker project using a case-cohort study including 14 cohorts (n = 1696 cases and 2926 subcohort representatives), and in the Nodule Malignancy project within five LDCT screening studies (n = 675 cases, 680 benign-nodule controls, and 648 nodule-free controls). Future progress to advance lung cancer early detection biomarkers will require carefully designed validation, translational, and comparative studies.

Original language	English (US)
Pages (from-to)	1-12
Number of pages	12
Journal	Annals of Epidemiology
Volume	77
DOIs	https://doi.org/10.1016/j.annepidem.2022.10.014
State	Published - Jan 2023

Keywords

Lung cancer screening
biomarker discovery and validation
biomarkers
early detection
nodule malignancy
risk prediction
study design

ASJC Scopus subject areas

Epidemiology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.annepidem.2022.10.014

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Robbins, H. A., Alcala, K., Moez, E. K., Guida, F., Thomas, S., Zahed, H., Warkentin, M. T., Smith-Byrne, K., Brhane, Y., Muller, D., Feng, X., Albanes, D., Aldrich, M. C., Arslan, A. A., Bassett, J., Berg, C. D., Cai, Q., Chen, C., Davies, M. P. A., ... Hung, R. J. (2023). Design and methodological considerations for biomarker discovery and validation in the Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Program. Annals of Epidemiology, 77, 1-12. https://doi.org/10.1016/j.annepidem.2022.10.014

Robbins, HA, Alcala, K, Moez, EK, Guida, F, Thomas, S, Zahed, H, Warkentin, MT, Smith-Byrne, K, Brhane, Y, Muller, D, Feng, X, Albanes, D, Aldrich, MC, Arslan, AA, Bassett, J, Berg, CD, Cai, Q, Chen, C, Davies, MPA, Diergaarde, B, Field, JK, Freedman, ND, Huang, WY, Johansson, M, Jones, M, Koh, WP, Lam, S, Lan, Q, Langhammer, A, Liao, LM, Liu, G, Malekzadeh, R, Milne, RL, Montuenga, LM, Rohan, T, Sesso, HD, Severi, G, Sheikh, M, Sinha, R, Shu, XO, Stevens, VL, Tammemägi, MC, Tinker, LF, Visvanathan, K, Wang, Y, Wang, R, Weinstein, SJ, White, E, Wilson, D, Yuan, JM, Zhang, X, Zheng, W, Amos, CI, Brennan, P, Johansson, M & Hung, RJ 2023, 'Design and methodological considerations for biomarker discovery and validation in the Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Program', Annals of Epidemiology, vol. 77, pp. 1-12. https://doi.org/10.1016/j.annepidem.2022.10.014

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title = "Design and methodological considerations for biomarker discovery and validation in the Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Program",

abstract = "The Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) program is an NCI-funded initiative with an objective to develop tools to optimize low-dose CT (LDCT) lung cancer screening. Here, we describe the rationale and design for the Risk Biomarker and Nodule Malignancy projects within INTEGRAL. The overarching goal of these projects is to systematically investigate circulating protein markers to include on a panel for use (i) pre-LDCT, to identify people likely to benefit from screening, and (ii) post-LDCT, to differentiate benign versus malignant nodules. To identify informative proteins, the Risk Biomarker project measured 1161 proteins in a nested-case control study within 2 prospective cohorts (n = 252 lung cancer cases and 252 controls) and replicated associations for a subset of proteins in 4 cohorts (n = 479 cases and 479 controls). Eligible participants had a current or former history of smoking and cases were diagnosed up to 3 years following blood draw. The Nodule Malignancy project measured 1078 proteins among participants with a heavy smoking history within four LDCT screening studies (n = 425 cases diagnosed up to 5 years following blood draw, 430 benign-nodule controls, and 398 nodule-free controls). The INTEGRAL panel will enable absolute quantification of 21 proteins. We will evaluate its performance in the Risk Biomarker project using a case-cohort study including 14 cohorts (n = 1696 cases and 2926 subcohort representatives), and in the Nodule Malignancy project within five LDCT screening studies (n = 675 cases, 680 benign-nodule controls, and 648 nodule-free controls). Future progress to advance lung cancer early detection biomarkers will require carefully designed validation, translational, and comparative studies.",

keywords = "Lung cancer screening, biomarker discovery and validation, biomarkers, early detection, nodule malignancy, risk prediction, study design",

author = "Robbins, {Hilary A.} and Karine Alcala and Moez, {Elham Khodayari} and Florence Guida and Sera Thomas and Hana Zahed and Warkentin, {Matthew T.} and Karl Smith-Byrne and Yonathan Brhane and David Muller and Xiaoshuang Feng and Demetrius Albanes and Aldrich, {Melinda C.} and Arslan, {Alan A.} and Julie Bassett and Berg, {Christine D.} and Qiuyin Cai and Chu Chen and Davies, {Michael P.A.} and Brenda Diergaarde and Field, {John K.} and Freedman, {Neal D.} and Huang, {Wen Yi} and Mikael Johansson and Michael Jones and Koh, {Woon Puay} and Stephen Lam and Qing Lan and Arnulf Langhammer and Liao, {Linda M.} and Geoffrey Liu and Reza Malekzadeh and Milne, {Roger L.} and Montuenga, {Luis M.} and Thomas Rohan and Sesso, {Howard D.} and Gianluca Severi and Mahdi Sheikh and Rashmi Sinha and Shu, {Xiao Ou} and Stevens, {Victoria L.} and Tammem{\"a}gi, {Martin C.} and Tinker, {Lesley F.} and Kala Visvanathan and Ying Wang and Renwei Wang and Weinstein, {Stephanie J.} and Emily White and David Wilson and Yuan, {Jian Min} and Xuehong Zhang and Wei Zheng and Amos, {Christopher I.} and Paul Brennan and Mattias Johansson and Hung, {Rayjean J.}",

note = "Publisher Copyright: {\textcopyright} 2022",

year = "2023",

month = jan,

doi = "10.1016/j.annepidem.2022.10.014",

language = "English (US)",

volume = "77",

pages = "1--12",

journal = "Annals of Epidemiology",

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TY - JOUR

T1 - Design and methodological considerations for biomarker discovery and validation in the Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Program

AU - Robbins, Hilary A.

AU - Alcala, Karine

AU - Moez, Elham Khodayari

AU - Guida, Florence

AU - Thomas, Sera

AU - Zahed, Hana

AU - Warkentin, Matthew T.

AU - Smith-Byrne, Karl

AU - Brhane, Yonathan

AU - Muller, David

AU - Feng, Xiaoshuang

AU - Albanes, Demetrius

AU - Aldrich, Melinda C.

AU - Arslan, Alan A.

AU - Bassett, Julie

AU - Berg, Christine D.

AU - Cai, Qiuyin

AU - Chen, Chu

AU - Davies, Michael P.A.

AU - Diergaarde, Brenda

AU - Field, John K.

AU - Freedman, Neal D.

AU - Huang, Wen Yi

AU - Johansson, Mikael

AU - Jones, Michael

AU - Koh, Woon Puay

AU - Lam, Stephen

AU - Lan, Qing

AU - Langhammer, Arnulf

AU - Liao, Linda M.

AU - Liu, Geoffrey

AU - Malekzadeh, Reza

AU - Milne, Roger L.

AU - Montuenga, Luis M.

AU - Rohan, Thomas

AU - Sesso, Howard D.

AU - Severi, Gianluca

AU - Sheikh, Mahdi

AU - Sinha, Rashmi

AU - Shu, Xiao Ou

AU - Stevens, Victoria L.

AU - Tammemägi, Martin C.

AU - Tinker, Lesley F.

AU - Visvanathan, Kala

AU - Wang, Ying

AU - Wang, Renwei

AU - Weinstein, Stephanie J.

AU - White, Emily

AU - Wilson, David

AU - Yuan, Jian Min

AU - Zhang, Xuehong

AU - Zheng, Wei

AU - Amos, Christopher I.

AU - Brennan, Paul

AU - Johansson, Mattias

AU - Hung, Rayjean J.

PY - 2023/1

Y1 - 2023/1

N2 - The Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) program is an NCI-funded initiative with an objective to develop tools to optimize low-dose CT (LDCT) lung cancer screening. Here, we describe the rationale and design for the Risk Biomarker and Nodule Malignancy projects within INTEGRAL. The overarching goal of these projects is to systematically investigate circulating protein markers to include on a panel for use (i) pre-LDCT, to identify people likely to benefit from screening, and (ii) post-LDCT, to differentiate benign versus malignant nodules. To identify informative proteins, the Risk Biomarker project measured 1161 proteins in a nested-case control study within 2 prospective cohorts (n = 252 lung cancer cases and 252 controls) and replicated associations for a subset of proteins in 4 cohorts (n = 479 cases and 479 controls). Eligible participants had a current or former history of smoking and cases were diagnosed up to 3 years following blood draw. The Nodule Malignancy project measured 1078 proteins among participants with a heavy smoking history within four LDCT screening studies (n = 425 cases diagnosed up to 5 years following blood draw, 430 benign-nodule controls, and 398 nodule-free controls). The INTEGRAL panel will enable absolute quantification of 21 proteins. We will evaluate its performance in the Risk Biomarker project using a case-cohort study including 14 cohorts (n = 1696 cases and 2926 subcohort representatives), and in the Nodule Malignancy project within five LDCT screening studies (n = 675 cases, 680 benign-nodule controls, and 648 nodule-free controls). Future progress to advance lung cancer early detection biomarkers will require carefully designed validation, translational, and comparative studies.

AB - The Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) program is an NCI-funded initiative with an objective to develop tools to optimize low-dose CT (LDCT) lung cancer screening. Here, we describe the rationale and design for the Risk Biomarker and Nodule Malignancy projects within INTEGRAL. The overarching goal of these projects is to systematically investigate circulating protein markers to include on a panel for use (i) pre-LDCT, to identify people likely to benefit from screening, and (ii) post-LDCT, to differentiate benign versus malignant nodules. To identify informative proteins, the Risk Biomarker project measured 1161 proteins in a nested-case control study within 2 prospective cohorts (n = 252 lung cancer cases and 252 controls) and replicated associations for a subset of proteins in 4 cohorts (n = 479 cases and 479 controls). Eligible participants had a current or former history of smoking and cases were diagnosed up to 3 years following blood draw. The Nodule Malignancy project measured 1078 proteins among participants with a heavy smoking history within four LDCT screening studies (n = 425 cases diagnosed up to 5 years following blood draw, 430 benign-nodule controls, and 398 nodule-free controls). The INTEGRAL panel will enable absolute quantification of 21 proteins. We will evaluate its performance in the Risk Biomarker project using a case-cohort study including 14 cohorts (n = 1696 cases and 2926 subcohort representatives), and in the Nodule Malignancy project within five LDCT screening studies (n = 675 cases, 680 benign-nodule controls, and 648 nodule-free controls). Future progress to advance lung cancer early detection biomarkers will require carefully designed validation, translational, and comparative studies.

KW - Lung cancer screening

KW - biomarker discovery and validation

KW - biomarkers

KW - early detection

KW - nodule malignancy

KW - risk prediction

KW - study design

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AN - SCOPUS:85141982446

SN - 1047-2797

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JO - Annals of Epidemiology

JF - Annals of Epidemiology

ER -

Design and methodological considerations for biomarker discovery and validation in the Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Program

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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