Mikolaskova Iveta, Zvarik Milan, Szaboova Kinga, Tibenska Elena, Durmanova Vladimira, Suchankova Magda, Kollarik Boris, Hesko Patrik, Palacka Patrik, Bucova Maria, Hunakova Luba
Institute of Immunology, Faculty of Medicine, Comenius University in Bratislava, Odborarske namestie 14, 811 08 Bratislava, Slovakia.
Department of Nuclear Physics and Biophysics, Faculty of Mathematics, Physics and Computer Science, Comenius University in Bratislava, Mlynska dolina F1, 842 48 Bratislava, Slovakia.
Int J Mol Sci. 2024 Nov 27;25(23):12765. doi: 10.3390/ijms252312765.
Stress responses can impact bladder cancer (BC) outcomes via immune-inflammatory pathway modulation. This study explores heart rate variability (HRV) associations with serum immune-inflammatory biomarkers, blood count inflammatory markers, and psychosocial self-report measures in patients versus healthy controls. The TREM-1 and TREM-2 expressions on peripheral blood monocytes were analysed via flow cytometry; serum inflammatory biomarkers by ELISA; HRV (5-min ECG) pre-tumour resection; blood counts by haematology analyser; and psychosocial factors by validated questionnaires. Patients exhibited altered immune-inflammatory profiles with increased TREM-1/TREM-2, sTREM-1, sTREM-1/sTREM-2 ratio, BDNF, MCP-1, and NLR, and reduced IFN-γ, IL-10, LMR, and PMR. HRV analysis indicated sympathetic dominance (SNS, Stress indices, ACmod) and reduced parasympathetic modulation (PNS index, SDNN, RMSSD, 2UV%, DCmod, SD1). Sympathetic HRV indices correlated positively with sTREM-1, sTREM-1/sTREM-2 ratio, fractalkine, and inflammatory markers (SII, NLR, PLR) and negatively with parasympathetic HRV indices-correlations absent in controls. Only in patients, reduced physical function and social support, and higher anxiety, depression, and fatigue, associated positively with sympathetic HRV indices and inflammatory markers. This study links immune-inflammatory markers, HRV parameters, and psychosocial factors in BC, suggesting that immune and autonomic variations may relate to unfavourable outcomes. Incorporating these assessments could help tailor more personalised treatment strategies for BC patients.
应激反应可通过调节免疫炎症途径影响膀胱癌（BC）的预后。本研究探讨了患者与健康对照者的心率变异性（HRV）与血清免疫炎症生物标志物、血细胞计数炎症标志物以及心理社会自我报告指标之间的关联。通过流式细胞术分析外周血单核细胞上的触发受体表达分子1（TREM-1）和触发受体表达分子2（TREM-2）；通过酶联免疫吸附测定法检测血清炎症生物标志物；在肿瘤切除术前通过5分钟心电图记录HRV；通过血液分析仪检测血细胞计数；并通过经过验证的问卷评估心理社会因素。患者表现出免疫炎症特征改变，TREM-1/TREM-2、可溶性TREM-1（sTREM-1）、sTREM-1/sTREM-2比值、脑源性神经营养因子（BDNF）、单核细胞趋化蛋白-1（MCP-1）和中性粒细胞与淋巴细胞比值（NLR）升高，而干扰素-γ（IFN-γ）、白细胞介素-10（IL-10）、淋巴细胞与单核细胞比值（LMR）和血小板与淋巴细胞比值（PMR）降低。HRV分析表明交感神经占优势（交感神经系统、应激指数、交流电调制）且副交感神经调节降低（副交感神经系统指数、正常窦性RR间期标准差（SDNN）、相邻RR间期差值的均方根（RMSSD）、三角指数（2UV%）、直流电调制、SD1）。交感神经HRV指标与sTREM-1、sTREM-1/sTREM-2比值、 fractalkine和炎症标志物（全身炎症反应指数（SII）、NLR、血小板与淋巴细胞比值（PLR））呈正相关，与副交感神经HRV指标呈负相关，而对照组不存在这种相关性。仅在患者中，身体功能和社会支持降低，焦虑、抑郁和疲劳程度较高，这些与交感神经HRV指标和炎症标志物呈正相关。本研究将BC中的免疫炎症标志物、HRV参数和心理社会因素联系起来，表明免疫和自主神经变化可能与不良预后有关。纳入这些评估有助于为BC患者制定更个性化的治疗策略。
