Ridner Sheila H, Dietrich Mary S, Sonis Stephen T, Murphy Barbara
1 Vanderbilt University School of Nursing , Nashville, Tennessee.
2 Department of Biostatistics, Vanderbilt University School of Medicine , Nashville, Tennessee.
Lymphat Res Biol. 2018 Nov 28;16(6):516-24. doi: 10.1089/lrb.2017.0074.
This study examined interrelationships of selected interleukins (ILs), tumor growth factors, matrix metalloproteinases (MMPs), and C-reactive protein, interferon-gamma (IFN-γ), and tumor necrosis factor α (TNF-α) with lymphedema/fibrosis in patients with head and neck cancer (HNC).
Patients newly diagnosed with ≥Stage II HNC (N = 100) were assessed for external/internal lymphedema and/or fibrosis before treatment, end-of-treatment, and at regularly established intervals through 72 weeks posttreatment and blood was drawn. Data from 83 patients were analyzed. Group-based trajectory modeling generated patient groups with similar longitudinal biomarker and lymphedema-fibrosis trajectories. Area-under-the-curve (AUC) values were also generated for each biomarker and severity of lymphedema-fibrosis. Associations among and between biomarkers and lymphedema-fibrosis trajectories and AUCs were tested (log-likelihood chi-square, correlations). The strongest evidence for the association of biomarkers with the overall and trajectory patterns and severity of lymphedema-fibrosis was observed for IL-6, IL-1β, TNF-α, TGF-β1, and MMP-9 (all p < 0.05). Convergence of joint trajectory patterns and AUC were observed with IL-6 with all lymphedema-fibrosis trajectories and internal lymphedema AUC. IL-1β trajectories converged with external lymphedema trajectories and all lymphedema-fibrosis AUCs. TNF-α and TGF-β1 converged most strongly with fibrosis in terms of trajectory patterns. However TNF-α demonstrated stronger association with lymphedema-fibrosis AUC (fibrosis: r = 0.49). MMP-9 demonstrated convergence with lymphedema-fibrosis AUCs (lymphedema: 0.43-0.42; fibrosis: 0.35).
Systemic levels of selected mediators of proinflammatory processes track with acute and chronic clinical phenotypes of lymphedema/fibrosis in HNC patients suggesting their potential role in the pathogenesis of these conditions.
本研究探讨了头颈部癌（HNC）患者中特定白细胞介素（ILs）、肿瘤生长因子、基质金属蛋白酶（MMPs）、C反应蛋白、干扰素-γ（IFN-γ）和肿瘤坏死因子α（TNF-α）与淋巴水肿/纤维化之间的相互关系。
对新诊断为≥II期HNC的患者（N = 100）在治疗前、治疗结束时以及治疗后72周内定期进行外部/内部淋巴水肿和/或纤维化评估，并采集血液样本。对83例患者的数据进行分析。基于组的轨迹模型生成了具有相似纵向生物标志物和淋巴水肿-纤维化轨迹的患者组。还为每个生物标志物和淋巴水肿-纤维化的严重程度生成了曲线下面积（AUC）值。测试了生物标志物之间以及与淋巴水肿-纤维化轨迹和AUC之间的关联（对数似然卡方检验、相关性）。观察到IL-6、IL-1β、TNF-α、TGF-β1和MMP-9与淋巴水肿-纤维化的总体及轨迹模式和严重程度之间存在关联的最强证据（所有p < 0.05）。观察到IL-6与所有淋巴水肿-纤维化轨迹和内部淋巴水肿AUC的联合轨迹模式和AUC的收敛。IL-1β轨迹与外部淋巴水肿轨迹和所有淋巴水肿-纤维化AUC收敛。就轨迹模式而言，TNF-α和TGF-β1与纤维化的收敛最为强烈。然而，TNF-α与淋巴水肿-纤维化AUC的关联更强（纤维化：r = 0.49）。MMP-9与淋巴水肿-纤维化AUC收敛（淋巴水肿：0.43 - 0.42；纤维化：0.35）。
促炎过程的特定介质的全身水平与HNC患者淋巴水肿/纤维化的急性和慢性临床表型相关，表明它们在这些病症的发病机制中具有潜在作用。
