Psychoneurological symptom clusters are co-occurring and interrelated physiological symptoms that may include cancer-related fatigue, pain, depressive symptoms, cognitive disturbances, and sleep disturbances. These symptoms are hypothesized to share a common systemic proinflammatory etiology. Thus, an investigation of systemic immune biomarkers is an important approach to test this hypothesis. Here, we investigated the associations between extracellular vesicle (EV)-associated and soluble cytokines with immune markers and symptom clusters in men with non-metastatic prostate cancer. This observational study included 40 men with non-metastatic prostate cancer at the start (T1) of external beam radiation therapy (EBRT) and 3 months post treatment (T2), as well as 20 men with non-metastatic prostate cancer on active surveillance (AS) seen at one time point. Collected questionnaires assessed patient-reported fatigue, sleep disturbances, depressive symptoms, and cognitive fatigue. In total, 45 soluble and EV-associated biomarkers in plasma were determined by multiplex assays. Principal component analysis (PCA) was used to identify psychoneurological symptom clusters for each study group and their time points. Bivariate correlation analysis was run for each identified PCA cluster with the concentrations of EV-associated and soluble cytokines and immune markers. Both EV-associated and soluble forms of RANTES significantly correlated with the symptom cluster for EBRT at T1, whereas, at T2, soluble IFNα2, IL-9, and IL-17 correlated with the corresponding symptom cluster. For the AS group, soluble survivin correlated with psychoneurological symptoms. Linking specific inflammatory cytokines with psychoneurological symptom clusters in men receiving prostate cancer treatment can enhance understanding of the underlying mechanisms of this phenomenon and aid in developing targeted interventions.

精神神经症状群是同时发生且相互关联的生理症状，可能包括癌症相关的疲劳、疼痛、抑郁症状、认知障碍和睡眠障碍。假设这些症状具有共同的全身性促炎病因。因此，对全身免疫生物标志物的研究是检验这一假设的重要方法。在这里，我们研究了非转移性前列腺癌男性中细胞外囊泡 (EV) 相关细胞因子和可溶性细胞因子与免疫标记物和症状群之间的关联。这项观察性研究包括 40 名在外照射放射治疗 (EBRT) 开始时 (T1​​) 和治疗后 3 个月 (T2) 的非转移性前列腺癌男性，以及 20 名接受主动监测的非转移性前列腺癌男性。 AS）在某个时间点看到。收集的问卷评估了患者报告的疲劳、睡眠障碍、抑郁症状和认知疲劳。通过多重测定总共测定了血浆中 45 种可溶性和 EV 相关生物标志物。主成分分析（PCA）用于识别每个研究组的精神神经症状群及其时间点。对每个确定的 PCA 簇与 EV 相关和可溶性细胞因子和免疫标记物的浓度进行双变量相关分析。 EV 相关型和可溶性 RANTES 形式均与 T1 时 EBRT 的症状群显着相关，而在 T2 时，可溶性 IFNα2、IL-9 和 IL-17 与相应的症状群相关。对于 AS 组，可溶性生存素与精神神经症状相关。 将接受前列腺癌治疗的男性的特定炎症细胞因子与心理神经症状群联系起来，可以增强对这种现象的潜在机制的理解，并有助于制定有针对性的干预措施。