Lin Yufen, Peng Gang, Bruner Deborah W, Miller Andrew H, Saba Nabil F, Higgins Kristin A, Shin Dong M, Claussen Henry, Johnston H Richard, Houser Madelyn C, Wommack Evanthia C, Xiao Canhua
Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, USA; Winship Cancer Institute, Emory University, Atlanta, USA.
Department of Medical and Molecular Genetics, School of Medicine, Indiana University, Indianapolis, USA.
J Psychosom Res. 2023 Dec;175:111518. doi: 10.1016/j.jpsychores.2023.111518. Epub 2023 Oct 10.
Patients with head and neck cancer (HNC) experience psychoneurological symptoms (PNS, i.e., depression, fatigue, sleep disturbance, pain, and cognitive dysfunction) during intensity-modulated radiotherapy (IMRT) that negatively impact their functional status, quality of life, and overall survival. The underlying mechanisms for PNS are still not fully understood. This study aimed to examine differentially expressed genes and pathways related to PNS for patients undergoing IMRT (i.e., before, end of, 6 months, and 12 months after IMRT).
Participants included 142 patients with HNC (mean age 58.9 ± 10.3 years, 72.5% male, 83.1% White). Total RNA extracted from blood leukocytes were used for genome-wide gene expression assays. Linear mixed effects model was used to examine the association between PNS and gene expression across time. Gene Ontology (GO) enrichment analysis was employed to identify pathways related to PNS.
A total of 1352 genes (162 upregulated, 1190 downregulated) were significantly associated with PNS across time (false discovery rate (FDR) < 0.05). Among these genes, 112 GO terms were identified (FDR < 0.05). The top 20 GO terms among the significant upregulated genes were related to immune and inflammatory responses, while the top 20 GO terms among the significant downregulated genes were associated with telomere maintenance.
This study is the first to identify genes and pathways linked to immune and inflammatory responses and telomere maintenance that are associated with PNS in patients with HNC receiving IMRT. Inflammation and aging markers may be candidate biomarkers for PNS. Understanding biological markers may produce targets for novel interventions.
头颈癌（HNC）患者在调强放射治疗（IMRT）期间会出现精神神经症状（PNS，即抑郁、疲劳、睡眠障碍、疼痛和认知功能障碍），这些症状会对其功能状态、生活质量和总生存期产生负面影响。PNS的潜在机制仍未完全明确。本研究旨在检测接受IMRT的患者（即IMRT前、IMRT结束时、IMRT后6个月和12个月）与PNS相关的差异表达基因和通路。
研究对象包括142例HNC患者（平均年龄58.9±10.3岁，72.5%为男性，83.1%为白人）。从血液白细胞中提取的总RNA用于全基因组基因表达分析。采用线性混合效应模型检测PNS与不同时间点基因表达之间的关联。利用基因本体（GO）富集分析确定与PNS相关的通路。
共有1352个基因（162个上调，1190个下调）在不同时间与PNS显著相关（错误发现率（FDR）<0.05）。在这些基因中，鉴定出112个GO术语（FDR<0.05）。显著上调基因中的前20个GO术语与免疫和炎症反应相关，而显著下调基因中的前20个GO术语与端粒维持相关。
本研究首次鉴定出与免疫和炎症反应以及端粒维持相关的基因和通路，这些基因和通路与接受IMRT的HNC患者的PNS有关。炎症和衰老标志物可能是PNS的候选生物标志物。了解生物标志物可能为新型干预措施提供靶点。
