目的:内源性大麻素(eCBs)参与各种生理功能,如食欲,新陈代谢,和炎症。尽管在难治性癌症恶病质(RCC)患者中经常观察到这些功能的恶化,循环eCBs与癌症恶病质之间的关系尚不清楚.本研究旨在评估肾癌患者eCBs循环水平与临床表现之间的关系。
方法:循环N-花生四烯酸乙醇胺(anandamide,在39例RCC患者中测量了AEA)和2-花生四酰基甘油(2-AG)水平(36%的女性,中位年龄和IQR:79和69-85),18名年龄和性别相匹配的对照者接受了非传染性疾病的药物治疗,使用液相色谱与串联质谱。在RCC组中,eCB水平与临床发现之间的关系-如厌食症,疼痛的意识,性能状态,和生存期-也进行了检查。由于抗炎药可以影响eCBs的作用和代谢,进行了以下两项分析。在分析1中,所有参与者都包括在内,在分析2中,接受任何抗炎药的参与者被排除.
结果:在两种分析中,RCC组的血清AEA和2-AG水平是对照组的两倍以上。在分析1中,只有8%的患者报告使用数字评定量表(NRS)评估的食欲正常,血清AEA水平与NRS评分呈负相关(R=-0.498,p=0.001)。血清2-AG水平与血清甘油三酯水平呈正相关(R=0.419,p=0.008)。AEA和2-AG水平均与血清C反应蛋白(CRP)水平呈正相关(AEA:R=0.516,p<0.001;2-AG:R=0.483,p=0.002)。以逐步程序的形式进行多元线性回归分析;NRS评分和CRP水平显示与AEA水平显着相关(NRS:p=0.001;CRP:p<0.001),调整后的R2值为0.426。同样,甘油三酯和CRP水平显示与2-AG水平的对数显著相关(甘油三酯:p<0.001;CRP:p<0.001),调整后的R2值为0.442。在分析2中,血清AEA水平与NRS评分呈负相关(R=-0.757,p<0.001)。而血清甘油三酯水平与2-AG水平呈正相关(R=0.623,p=0.010)。
结论:肾癌患者的循环eCB水平明显高于对照组。在RCC患者中,循环AEA可能在厌食症中起作用,而2-AG可能在血清甘油三酯水平中起作用。
Endocannabinoids (eCBs) are involved in various physiological functions such as appetite, metabolism, and inflammation. Although deterioration of these functions is often observed in patients with refractory cancer cachexia (RCC), the relationship between circulating eCBs and cancer cachexia remains unknown. This
study aimed to evaluate the relationship between circulating levels of eCBs and clinical findings in patients with RCC.
Circulating N-arachidonoylethanolamine (anandamide, AEA) and 2-arachidonoylglycerol (2-AG) levels were measured in 39 patients with RCC (36% females, median age and IQR: 79 and 69-85), and 18 age- and sex-matched controls who received medical therapy for non-communicable diseases, using liquid chromatography with tandem mass spectrometry. In the RCC group, relationships between eCB levels and clinical findings-such as anorexia, awareness of pain, performance status, and survival period-were also examined. As anti-inflammatory drugs can influence the action and metabolism of eCBs, the following two analyses were conducted. In analysis 1, all participants were included, and in analysis 2, participants receiving any anti-inflammatory drugs were excluded.
Serum AEA and 2-AG levels were more than twice as high in the RCC group than in those in the control group in both analyses. In analysis 1, only 8% of patients reported normal appetite assessed using the numerical rating scale (NRS), and serum AEA levels were negatively correlated with the NRS scores (R = -0.498, p = 0.001). Serum 2-AG levels were positively correlated with serum triglyceride levels (R = 0.419, p = 0.008). Both AEA and 2-AG levels were positively correlated with serum C-reactive protein (CRP) levels (AEA: R = 0.516, p < 0.001; 2-AG: R = 0.483, p = 0.002). Multiple linear regression analysis in the form of a stepwise procedure was performed; NRS scores and CRP levels showed a significant association with AEA levels (NRS: p = 0.001; CRP: p < 0.001), with an adjusted R2 value of 0.426. Similarly, triglyceride and CRP levels showed a significant association with the log of 2-AG levels (triglycerides: p < 0.001; CRP: p < 0.001), with an adjusted R2 value of 0.442. In analysis 2, serum AEA levels were negatively correlated with the NRS scores (R = -0.757, p < 0.001), whereas serum triglyceride levels were positively correlated with 2-AG levels (R = 0.623, p = 0.010).
Circulating eCB levels were significantly higher in patients with RCC than those in controls. In patients with RCC, circulating AEA may play a role in anorexia, whereas 2-AG may play a role in serum triglyceride levels.