PO.CL11.02 · 临床研究

疼痛严重程度与OSCC中侵袭性疾病及不良生存所涉及的分子通路相关

Pain severity is related to molecular pathways underlying aggressive disease and poor survival in OSCC

编号 1240 展板 14 时间 4/19 02:00–05:00 区域 Section 48 主讲 Minh Phuong Dong, PhD

分会场 Survivorship, Supportive Care, and Quality of Life in Oncology

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作者与单位 Authors & Affiliations

Minh Phuong Dong¹, Gary Yu², Michele Arambula¹, Bac An Luong¹, Paul Walker¹, Traeden Wilson¹, Khanh Nguyen¹, Carissa M. Thomas³, Yi Ye⁴, Bradley Aouizerat⁴, Chi Viet⁵

¹Loma Linda University, Loma Linda, CA,²Columbia University, New York, NY,³University of Colorado, Aurora, CO,⁴New York University, New York, NY,⁵Loma Linda University, Loma Linda, NY

摘要 Abstract

中文摘要

疼痛是口腔鳞状细胞癌（OSCC）患者所经历的最严重症状之一，会损害患者的功能和生活质量。然而其临床和分子决定因素仍然定义不清。本研究的目的是探究疼痛、生活质量（QoL）和肿瘤生物学如何交织在一起，以改善预后判断和以患者为中心的护理。这项前瞻性多机构研究纳入了来自Loma Linda University（LLU）和University of Alabama at Birmingham（UAB）的196例OSCC患者。采用UCSF口腔癌疼痛问卷和简明疼痛量表（BPI）评估疼痛。采用EORTC QLQ-C30/H&N35刻画功能和症状障碍（QoL）。手术时采集速冻肿瘤进行RNA-Seq。数据采用Spearman相关、Wilcoxon、Kruskal-Wallis检验、ANCOVA、Kaplan-Meier对数秩检验和Cox风险回归进行分析。我们的结果显示，报告高疼痛的患者总体QoL显著更低，包括功能评分降低（躯体、角色、情绪、认知和社会功能）和症状负担更高（p < 0.05），且完全独立于其诊断时的癌症分期。此外，吗啡毫克当量（MME/天）与疼痛严重程度及更差的QoL指标强相关（p < 0.05）。Kaplan-Meier分析显示，高疼痛（UCSF和BPI）、更高的症状评分、更高的H&N35评分、更低的总体健康状况评分和功能评分，以及阿片类药物使用，均与更差的生存相关（p < 0.05）。在校正混杂因素（年龄、性别、种族、病理分期、PNI、LVI、吸烟状态）后，Cox风险回归分析显示功能评分（HR = 0.5，95%CI [0.287-0.873]）、症状评分（HR = 2.144，95%CI [1.169-3.934]）、HN35评分（HR = 2.192，95%CI [1.195-4.023]）和阿片类药物使用（HR = 2.665，95%CI [1.510-4.706]）是生存的独立预测因素。对128例患者进行的RNAseq分析比较了高疼痛和低疼痛肿瘤，识别出与轴突生成、神经元间突触相关的GO通路显著富集，以及KEGG中涉及神经退行性变-多种疾病、阿尔茨海默病和亨廷顿病的通路。此外，低功能（低功能评分）患者中排名靠前的失调GO通路为胞质翻译、核糖体生物合成，以及p53类介导因子对信号转导的调控。总之，这些发现表明，在OSCC中疼痛严重程度、阿片类药物需求和生活质量下降与侵袭性肿瘤特征及更差的生存密切相关。分子分析凸显了神经相关失调在OSCC疼痛中的潜在作用。

查看英文原文 English abstract

Pain is one of the worst symptoms experienced by patients with oral squamous cell carcinoma (OSCC), which impairs patients' function and quality of life. Yet its clinical and molecular determinants remain poorly defined. The objective of this study was to investigate how pain, quality of life (QoL), and tumor biology intersect to improve prognostication and patient-centered care. This prospective multi-institutional study enrolled 196 OSCC patients from Loma Linda University (LLU) and the University of Alabama at Birmingham (UAB). Pain was assessed using the UCSF Oral Cancer Pain Questionnaire and, Brief Pain Inventory (BPI). Functional and symptom disturbance (QoL) were characterized using EORTC QLQ-C30/H&N35. Flash frozen tumors were collected at surgery for RNA-Seq. Data were analyzed using Spearman correlation, Wilcoxon, Kruskal-Wallis tests, ANCOVA, Kaplan-Meier log-rank test, and Cox hazard regression. Our results revealed that patients reporting high pain demonstrated significantly lower overall QoL, including reduced functional scores (physical, role, emotional, cognitive, and social functioning) and higher symptom burden (p<0.05), entirely independent of their cancer stage at diagnosis. Additionally, morphine milligram equivalents (MME/day) were strongly correlated with pain severity and worse QoL metrics (p<0.05). Kaplan-Meier analysis showed that high pain (UCSF and BPI), higher symptom score, and higher H&N35 score, lower global health status score and functional score, and opioid use were associated with worse survival (p<0.05). After adjustment for confounders (age, sex, race, pathologic stage, PNI, LVI, smoking status), Cox hazard regression analysis revealed functional score (HR = 0.5, CI 95% [0.287-0.873]), symptom score (HR = 2.144, CI 95% [1.169-3.934]), HN35 scores (HR = 2.192, CI 95% [1.195-4.023]) and opioid use (HR = 2.665, CI 95% [1.510-4.706]) as independent predictors of survival. RNAseq analysis of 128 patients comparing high- and low-pain tumors identified significant enrichment in GO pathways related to axonogenesis, neuron to neuron synapse, and in KEGG involved pathways of neurodegeneration-multiple disease, Alzheimer's, and Huntington's disease pathways. In addition, the top dysregulated GO pathways in patients with low function (low functional score) were cytoplasmic translation, ribosome biogenesis, and regulator of signal transduction by p53 class mediator. In conclusion, these findings demonstrated that pain severity, opioid requirement, and diminished quality of life are tightly linked to aggressive tumor features and poorer survival in OSCC. Molecular analyses highlight the potential of neural-associated dysregulation in OSCC pain.

利益披露 Disclosure

M. Dong, None.. G. Yu, None.. M. Arambula, None.. B. Luong, None.. P. Walker, None.. T. Wilson, None.. K. Nguyen, None.. C. M. Thomas, None.. Y. Ye, None.. B. Aouizerat, None.. C. Viet, None.

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