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
Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indianapolis, United States of America.
Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina, United States of America.
PLoS One. 2017 Sep 21;12(9):e0183239. doi: 10.1371/journal.pone.0183239. eCollection 2017.
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.
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.
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.
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.
背景/目的：放射治疗（RT）会刺激多种免疫体液因子的释放，这使得确定具有临床意义的细胞因子表达模式变得复杂。本研究采用主成分分析（PCA）来分析接受放疗的非小细胞肺癌（NSCLC）患者的细胞因子，并探讨在接受或未接受化疗的情况下，短程立体定向体部放疗（SBRT）和常规分割放疗（CFRT）后细胞因子变化的差异。
数据集包括141例按照前瞻性临床方案接受治疗的NSCLC患者；PCA基于128例在基线和治疗期间具有完整CK值的患者。患者接受SBRT（n = 16）、CFRT（n = 18）或联合化疗的CFRT（ChRT，n = 107）。在基线、放疗期间和放疗后，从前瞻性收集的少血小板血浆样本中检测30种细胞因子的水平。PCA用于研究各时间点患者细胞因子水平的变化。
患者中位年龄为66岁，22.7%为女性。PCA显示，sCD40l、fractalkine/C3、IP10、VEGF、IL-1α、IL-10和GMCSF是基线细胞因子水平变化的主要因素。在治疗期间，sCD40l、IP10、MIP-1β、fractalkine、IFN-γ和VEGF是细胞因子水平变化的主要因素。在SBRT患者中，最重要的因素是sCD40l、IP10和MIP-1β，而fractalkine在单纯CFRT患者中变化更大。ChRT患者除了IP10、MIP-1β和sCD40l外，IFN-γ和VEGF也有变化。
PCA可以识别分割放疗后潜在的重要细胞因子表达模式。我们的PCA显示，炎症细胞因子在放疗后细胞因子谱中占主导地位，SBRT与CFRT、有化疗与无化疗后的变化不同。计划进一步研究以验证这些发现，并确定PCA识别的细胞因子谱的临床意义。
