Dynamic expression of Schlafen 11 (SLFN11) in circulating tumour cells as a liquid biomarker in small cell lung cancer

Bingnan Zhang; C. Allison Stewart; Qi Wang; Robert J. Cardnell; Pedro Rocha; Junya Fujimoto; Luisa M. Solis Soto; Runsheng Wang; Veronica Novegil; Peter Ansell; Lei He; Luisa Fernandez; Adam Jendrisak; Cole Gilbertson; Joseph D. Schonhoft; Jiyun Byun; Joshua Jones; Amanda K.L. Anderson; Ana Aparicio; Hai Tran; Marcelo V. Negrao; Jianjun Zhang; Wei lien Wang; Ignacio I. Wistuba; Jing Wang; Rick Wenstrup; Lauren A. Byers; Carl M. Gay

doi:10.1038/s41416-022-01811-9

Dynamic expression of Schlafen 11 (SLFN11) in circulating tumour cells as a liquid biomarker in small cell lung cancer

Bingnan Zhang, C. Allison Stewart, Qi Wang, Robert J. Cardnell, Pedro Rocha, Junya Fujimoto, Luisa M. Solis Soto, Runsheng Wang, Veronica Novegil, Peter Ansell, Lei He, Luisa Fernandez, Adam Jendrisak, Cole Gilbertson, Joseph D. Schonhoft, Jiyun Byun, Joshua Jones, Amanda K.L. Anderson, Ana Aparicio, Hai TranMarcelo V. Negrao, Jianjun Zhang, Wei lien Wang, Ignacio I. Wistuba, Jing Wang, Rick Wenstrup, Lauren A. Byers, Carl M. Gay

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8 Scopus citations

Abstract

Introduction: Small cell lung cancer (SCLC) is an aggressive malignancy with no established biomarkers. Schlafen 11(SLFN11), a DNA/RNA helicase that sensitises cancer cells to DNA-damaging agents, has emerged as a promising predictive biomarker for several drug classes including platinum and PARP inhibitors. Detection of SLFN11 in circulating tumour cells (CTCs) may provide a valuable alternative to tissue sampling. Methods: SLFN11 expression was evaluated in tumour samples and characterised in circulating tumour cells (CTC) longitudinally to determine its potential role as a biomarker of response. Results: Among 196 SCLC tumours, 51% expressed SLFN11 by IHC. In addition, 20/29 extra-thoracic high-grade neuroendocrine tumours expressed SLFN11 expression. In 64 blood samples from 42 SCLC patients, 83% (53/64) of samples had detectable CTCs, and SLFN11-positive CTCs were detected in 55% (29/53). Patients actively receiving platinum treatment had the lowest number of CTCs and a lower percentage of SLFN11-positive CTCs (p = 0.014). Analysis from patients with longitudinal samples suggest a decrease in CTC number and in SLFN11 expression that correlates with clinical response. Conclusions: SLFN11 levels can be monitored in CTCs from SCLC patients using non-invasive liquid biopsies. The ability to detect SLFN11 in CTCs from SCLC patients adds a valuable tool for the detection and longitudinal monitoring of this promising biomarker.

Original language	English (US)
Pages (from-to)	569-576
Number of pages	8
Journal	British journal of cancer
Volume	127
Issue number	3
DOIs	https://doi.org/10.1038/s41416-022-01811-9
State	Published - Aug 1 2022

ASJC Scopus subject areas

Oncology
Cancer Research

MD Anderson CCSG core facilities

Bioinformatics Shared Resource

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10.1038/s41416-022-01811-9

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Zhang, B., Stewart, C. A., Wang, Q., Cardnell, R. J., Rocha, P., Fujimoto, J., Solis Soto, L. M., Wang, R., Novegil, V., Ansell, P., He, L., Fernandez, L., Jendrisak, A., Gilbertson, C., Schonhoft, J. D., Byun, J., Jones, J., Anderson, A. K. L., Aparicio, A., ... Gay, C. M. (2022). Dynamic expression of Schlafen 11 (SLFN11) in circulating tumour cells as a liquid biomarker in small cell lung cancer. British journal of cancer, 127(3), 569-576. https://doi.org/10.1038/s41416-022-01811-9

Zhang, B , Stewart, CA , Wang, Q , Cardnell, RJ, Rocha, P, Fujimoto, J, Solis Soto, LM, Wang, R, Novegil, V, Ansell, P, He, L, Fernandez, L, Jendrisak, A, Gilbertson, C, Schonhoft, JD, Byun, J, Jones, J, Anderson, AKL, Aparicio, A , Tran, H , Negrao, MV , Zhang, J , Wang, WL , Wistuba, II , Wang, J, Wenstrup, R, Byers, LA & Gay, CM 2022, 'Dynamic expression of Schlafen 11 (SLFN11) in circulating tumour cells as a liquid biomarker in small cell lung cancer', British journal of cancer, vol. 127, no. 3, pp. 569-576. https://doi.org/10.1038/s41416-022-01811-9

@article{4cc35d62a26d49d8a172b1fb3359c537,

title = "Dynamic expression of Schlafen 11 (SLFN11) in circulating tumour cells as a liquid biomarker in small cell lung cancer",

abstract = "Introduction: Small cell lung cancer (SCLC) is an aggressive malignancy with no established biomarkers. Schlafen 11(SLFN11), a DNA/RNA helicase that sensitises cancer cells to DNA-damaging agents, has emerged as a promising predictive biomarker for several drug classes including platinum and PARP inhibitors. Detection of SLFN11 in circulating tumour cells (CTCs) may provide a valuable alternative to tissue sampling. Methods: SLFN11 expression was evaluated in tumour samples and characterised in circulating tumour cells (CTC) longitudinally to determine its potential role as a biomarker of response. Results: Among 196 SCLC tumours, 51% expressed SLFN11 by IHC. In addition, 20/29 extra-thoracic high-grade neuroendocrine tumours expressed SLFN11 expression. In 64 blood samples from 42 SCLC patients, 83% (53/64) of samples had detectable CTCs, and SLFN11-positive CTCs were detected in 55% (29/53). Patients actively receiving platinum treatment had the lowest number of CTCs and a lower percentage of SLFN11-positive CTCs (p = 0.014). Analysis from patients with longitudinal samples suggest a decrease in CTC number and in SLFN11 expression that correlates with clinical response. Conclusions: SLFN11 levels can be monitored in CTCs from SCLC patients using non-invasive liquid biopsies. The ability to detect SLFN11 in CTCs from SCLC patients adds a valuable tool for the detection and longitudinal monitoring of this promising biomarker.",

author = "Bingnan Zhang and Stewart, {C. Allison} and Qi Wang and Cardnell, {Robert J.} and Pedro Rocha and Junya Fujimoto and {Solis Soto}, {Luisa M.} and Runsheng Wang and Veronica Novegil and Peter Ansell and Lei He and Luisa Fernandez and Adam Jendrisak and Cole Gilbertson and Schonhoft, {Joseph D.} and Jiyun Byun and Joshua Jones and Anderson, {Amanda K.L.} and Ana Aparicio and Hai Tran and Negrao, {Marcelo V.} and Jianjun Zhang and Wang, {Wei lien} and Wistuba, {Ignacio I.} and Jing Wang and Rick Wenstrup and Byers, {Lauren A.} and Gay, {Carl M.}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2022",

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doi = "10.1038/s41416-022-01811-9",

language = "English (US)",

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TY - JOUR

T1 - Dynamic expression of Schlafen 11 (SLFN11) in circulating tumour cells as a liquid biomarker in small cell lung cancer

AU - Zhang, Bingnan

AU - Stewart, C. Allison

AU - Wang, Qi

AU - Cardnell, Robert J.

AU - Rocha, Pedro

AU - Fujimoto, Junya

AU - Solis Soto, Luisa M.

AU - Wang, Runsheng

AU - Novegil, Veronica

AU - Ansell, Peter

AU - He, Lei

AU - Fernandez, Luisa

AU - Jendrisak, Adam

AU - Gilbertson, Cole

AU - Schonhoft, Joseph D.

AU - Byun, Jiyun

AU - Jones, Joshua

AU - Anderson, Amanda K.L.

AU - Aparicio, Ana

AU - Tran, Hai

AU - Negrao, Marcelo V.

AU - Zhang, Jianjun

AU - Wang, Wei lien

AU - Wistuba, Ignacio I.

AU - Wang, Jing

AU - Wenstrup, Rick

AU - Byers, Lauren A.

AU - Gay, Carl M.

PY - 2022/8/1

Y1 - 2022/8/1

N2 - Introduction: Small cell lung cancer (SCLC) is an aggressive malignancy with no established biomarkers. Schlafen 11(SLFN11), a DNA/RNA helicase that sensitises cancer cells to DNA-damaging agents, has emerged as a promising predictive biomarker for several drug classes including platinum and PARP inhibitors. Detection of SLFN11 in circulating tumour cells (CTCs) may provide a valuable alternative to tissue sampling. Methods: SLFN11 expression was evaluated in tumour samples and characterised in circulating tumour cells (CTC) longitudinally to determine its potential role as a biomarker of response. Results: Among 196 SCLC tumours, 51% expressed SLFN11 by IHC. In addition, 20/29 extra-thoracic high-grade neuroendocrine tumours expressed SLFN11 expression. In 64 blood samples from 42 SCLC patients, 83% (53/64) of samples had detectable CTCs, and SLFN11-positive CTCs were detected in 55% (29/53). Patients actively receiving platinum treatment had the lowest number of CTCs and a lower percentage of SLFN11-positive CTCs (p = 0.014). Analysis from patients with longitudinal samples suggest a decrease in CTC number and in SLFN11 expression that correlates with clinical response. Conclusions: SLFN11 levels can be monitored in CTCs from SCLC patients using non-invasive liquid biopsies. The ability to detect SLFN11 in CTCs from SCLC patients adds a valuable tool for the detection and longitudinal monitoring of this promising biomarker.

AB - Introduction: Small cell lung cancer (SCLC) is an aggressive malignancy with no established biomarkers. Schlafen 11(SLFN11), a DNA/RNA helicase that sensitises cancer cells to DNA-damaging agents, has emerged as a promising predictive biomarker for several drug classes including platinum and PARP inhibitors. Detection of SLFN11 in circulating tumour cells (CTCs) may provide a valuable alternative to tissue sampling. Methods: SLFN11 expression was evaluated in tumour samples and characterised in circulating tumour cells (CTC) longitudinally to determine its potential role as a biomarker of response. Results: Among 196 SCLC tumours, 51% expressed SLFN11 by IHC. In addition, 20/29 extra-thoracic high-grade neuroendocrine tumours expressed SLFN11 expression. In 64 blood samples from 42 SCLC patients, 83% (53/64) of samples had detectable CTCs, and SLFN11-positive CTCs were detected in 55% (29/53). Patients actively receiving platinum treatment had the lowest number of CTCs and a lower percentage of SLFN11-positive CTCs (p = 0.014). Analysis from patients with longitudinal samples suggest a decrease in CTC number and in SLFN11 expression that correlates with clinical response. Conclusions: SLFN11 levels can be monitored in CTCs from SCLC patients using non-invasive liquid biopsies. The ability to detect SLFN11 in CTCs from SCLC patients adds a valuable tool for the detection and longitudinal monitoring of this promising biomarker.

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JO - British journal of cancer

JF - British journal of cancer

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Dynamic expression of Schlafen 11 (SLFN11) in circulating tumour cells as a liquid biomarker in small cell lung cancer

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MD Anderson CCSG core facilities

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