Principal component analysis identifies patterns of cytokine expression in non-small cell lung cancer patients undergoing definitive radiation therapy

Susannah G. Ellsworth, Bryan M. Rabatic, Jie Chen, Jing Zhao, Jeffrey Campbell, Weili Wang, Wenhu Pi, Paul Stanton, Martha Matuszak, Shruti Jolly, Amy Miller, Feng Ming Kong

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background/Purpose: Radiation treatment (RT) stimulates the release of many immunohumoral factors, complicating the identification of clinically significant cytokine expression patterns. This study used principal component analysis (PCA) to analyze cytokines in non-small cell lung cancer (NSCLC) patients undergoing RT and explore differences in changes after hypofractionated stereotactic body radiation therapy (SBRT) and conventionally fractionated RT (CFRT) without or with chemotherapy. Methods: The dataset included 141 NSCLC patients treated on prospective clinical protocols; PCA was based on the 128 patients who had complete CK values at baseline and during treatment. Patients underwent SBRT (n = 16), CFRT (n = 18), or CFRT (n = 107) with concurrent chemotherapy (ChRT). Levels of 30 cytokines were measured from prospectively collected platelet-poor plasma samples at baseline, during RT, and after RT. PCA was used to study variations in cytokine levels in patients at each time point. Results: Median patient age was 66, and 22.7% of patients were female. PCA showed that sCD40l, fractalkine/C3, IP10, VEGF, IL-1a, IL-10, and GMCSF were responsible for most variability in baseline cytokine levels. During treatment, sCD40l, IP10, MIP-1b, fractalkine, IFN-r, and VEGF accounted for most changes in cytokine levels. In SBRT patients, the most important players were sCD40l, IP10, and MIP-1b, whereas fractalkine exhibited greater variability in CFRT alone patients. ChRT patients exhibited variability in IFN-γ and VEGF in addition to IP10, MIP-1b, and sCD40l. Conclusions: PCA can identify potentially significant patterns of cytokine expression after fractionated RT. Our PCA showed that inflammatory cytokines dominate post-treatment cytokine profiles, and the changes differ after SBRT versus CFRT, with vs without chemotherapy. Further studies are planned to validate these findings and determine the clinical significance of the cytokine profiles identified by PCA.

Original languageEnglish (US)
Article numbere0183239
JournalPloS one
Volume12
Issue number9
DOIs
StatePublished - Sep 2017

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Radiotherapy
radiotherapy
lung neoplasms
Principal Component Analysis
Non-Small Cell Lung Carcinoma
Principal component analysis
principal component analysis
cytokines
Cells
Cytokines
Chemokine CX3CL1
Radiation
Chemotherapy
cells
Vascular Endothelial Growth Factor A
drug therapy
Therapeutics
Drug Therapy
Background Radiation
Clinical Protocols

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Principal component analysis identifies patterns of cytokine expression in non-small cell lung cancer patients undergoing definitive radiation therapy. / Ellsworth, Susannah G.; Rabatic, Bryan M.; Chen, Jie; Zhao, Jing; Campbell, Jeffrey; Wang, Weili; Pi, Wenhu; Stanton, Paul; Matuszak, Martha; Jolly, Shruti; Miller, Amy; Kong, Feng Ming.

In: PloS one, Vol. 12, No. 9, e0183239, 09.2017.

Research output: Contribution to journalArticle

Ellsworth, SG, Rabatic, BM, Chen, J, Zhao, J, Campbell, J, Wang, W, Pi, W, Stanton, P, Matuszak, M, Jolly, S, Miller, A & Kong, FM 2017, 'Principal component analysis identifies patterns of cytokine expression in non-small cell lung cancer patients undergoing definitive radiation therapy', PloS one, vol. 12, no. 9, e0183239. https://doi.org/10.1371/journal.pone.0183239
Ellsworth, Susannah G. ; Rabatic, Bryan M. ; Chen, Jie ; Zhao, Jing ; Campbell, Jeffrey ; Wang, Weili ; Pi, Wenhu ; Stanton, Paul ; Matuszak, Martha ; Jolly, Shruti ; Miller, Amy ; Kong, Feng Ming. / Principal component analysis identifies patterns of cytokine expression in non-small cell lung cancer patients undergoing definitive radiation therapy. In: PloS one. 2017 ; Vol. 12, No. 9.
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abstract = "Background/Purpose: Radiation treatment (RT) stimulates the release of many immunohumoral factors, complicating the identification of clinically significant cytokine expression patterns. This study used principal component analysis (PCA) to analyze cytokines in non-small cell lung cancer (NSCLC) patients undergoing RT and explore differences in changes after hypofractionated stereotactic body radiation therapy (SBRT) and conventionally fractionated RT (CFRT) without or with chemotherapy. Methods: The dataset included 141 NSCLC patients treated on prospective clinical protocols; PCA was based on the 128 patients who had complete CK values at baseline and during treatment. Patients underwent SBRT (n = 16), CFRT (n = 18), or CFRT (n = 107) with concurrent chemotherapy (ChRT). Levels of 30 cytokines were measured from prospectively collected platelet-poor plasma samples at baseline, during RT, and after RT. PCA was used to study variations in cytokine levels in patients at each time point. Results: Median patient age was 66, and 22.7{\%} of patients were female. PCA showed that sCD40l, fractalkine/C3, IP10, VEGF, IL-1a, IL-10, and GMCSF were responsible for most variability in baseline cytokine levels. During treatment, sCD40l, IP10, MIP-1b, fractalkine, IFN-r, and VEGF accounted for most changes in cytokine levels. In SBRT patients, the most important players were sCD40l, IP10, and MIP-1b, whereas fractalkine exhibited greater variability in CFRT alone patients. ChRT patients exhibited variability in IFN-γ and VEGF in addition to IP10, MIP-1b, and sCD40l. Conclusions: PCA can identify potentially significant patterns of cytokine expression after fractionated RT. Our PCA showed that inflammatory cytokines dominate post-treatment cytokine profiles, and the changes differ after SBRT versus CFRT, with vs without chemotherapy. Further studies are planned to validate these findings and determine the clinical significance of the cytokine profiles identified by PCA.",
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AU - Ellsworth, Susannah G.

AU - Rabatic, Bryan M.

AU - Chen, Jie

AU - Zhao, Jing

AU - Campbell, Jeffrey

AU - Wang, Weili

AU - Pi, Wenhu

AU - Stanton, Paul

AU - Matuszak, Martha

AU - Jolly, Shruti

AU - Miller, Amy

AU - Kong, Feng Ming

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AB - Background/Purpose: Radiation treatment (RT) stimulates the release of many immunohumoral factors, complicating the identification of clinically significant cytokine expression patterns. This study used principal component analysis (PCA) to analyze cytokines in non-small cell lung cancer (NSCLC) patients undergoing RT and explore differences in changes after hypofractionated stereotactic body radiation therapy (SBRT) and conventionally fractionated RT (CFRT) without or with chemotherapy. Methods: The dataset included 141 NSCLC patients treated on prospective clinical protocols; PCA was based on the 128 patients who had complete CK values at baseline and during treatment. Patients underwent SBRT (n = 16), CFRT (n = 18), or CFRT (n = 107) with concurrent chemotherapy (ChRT). Levels of 30 cytokines were measured from prospectively collected platelet-poor plasma samples at baseline, during RT, and after RT. PCA was used to study variations in cytokine levels in patients at each time point. Results: Median patient age was 66, and 22.7% of patients were female. PCA showed that sCD40l, fractalkine/C3, IP10, VEGF, IL-1a, IL-10, and GMCSF were responsible for most variability in baseline cytokine levels. During treatment, sCD40l, IP10, MIP-1b, fractalkine, IFN-r, and VEGF accounted for most changes in cytokine levels. In SBRT patients, the most important players were sCD40l, IP10, and MIP-1b, whereas fractalkine exhibited greater variability in CFRT alone patients. ChRT patients exhibited variability in IFN-γ and VEGF in addition to IP10, MIP-1b, and sCD40l. Conclusions: PCA can identify potentially significant patterns of cytokine expression after fractionated RT. Our PCA showed that inflammatory cytokines dominate post-treatment cytokine profiles, and the changes differ after SBRT versus CFRT, with vs without chemotherapy. Further studies are planned to validate these findings and determine the clinical significance of the cytokine profiles identified by PCA.

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