Choromańska Barbara, Myśliwiec Piotr, Kozłowski Tomasz, Łuba Magdalena, Wojskowicz Piotr, Dadan Jacek, Myśliwiec Hanna, Choromańska Katarzyna, Makarewicz Katarzyna, Zalewska Anna, Maciejczyk Mateusz
1st Department of General and Endocrine Surgery, Medical University of Bialystok, Bialystok, Poland.
Department of Dermatology and Venereology, Medical University of Bialystok, Bialystok, Poland.
J Inflamm Res. 2021 Nov 30;14:6317-6330. doi: 10.2147/JIR.S337910. eCollection 2021.
Adrenal masses are the most common of all human tumors. The role of nitrosative stress and inflammation in cancer development has already been demonstrated. However, it is not known whether they are involved in the pathogenesis of adrenal tumors. The aim of the study was to investigate a cross-talk between nitrosative stress, inflammation and hypoxia-inducible factor (HIF-1α) in 75 patients with different types of adrenal masses (non-functional incidentaloma, pheochromocytoma and Cushing's/Conn's adenoma).
The plasma concentrations of total nitric oxide (NO), S-nitrosothiols, peroxynitrite nitrotyrosine and the activity of serum myeloperoxidase (MPO) were measured spectrophotometrically, whereas concentrations of interleukin 1 beta (IL-1β), tumor necrosis factor α (TNF-α) and hypoxia-inducible factor 1 alpha (HIF-1α) were measured using commercial ELISA kits. The control group consisted of 50 healthy people matched by age and sex to the study group. The number of subjects was determined a priori based on our previous experiment (power of the test = 0.9; α = 0.05).
We found significantly higher nitrosative stress (↑nitric oxide, ↑peroxynitrite, ↑S-nitrosothiols and ↑nitrotyrosine) in the plasma of patients with adrenal tumors, which was accompanied by increased inflammatory (↑myeloperoxidase, ↑interleukin 1 beta and ↑tumor necrosis factor α) and hypoxia (HIF-1α) biomarkers. Peroxynitrite and nitrotyrosine were positively correlated with aldosterone level. Nitrosative stress was also associated with inflammation and HIF-1α. Interestingly, plasma nitrotyrosine and serum MPO differentiated patients with adrenal tumor from healthy individuals with high sensitivity and specificity. Moreover, using multivariate regression analysis, we showed that ONOO and IL-1β depended on cortisol level, while ONOO, nitrotyrosine and HIF-1α were associated with aldosterone. Unfortunately, none of the assessed biomarkers differentiated between tumor types studied, suggesting that the severity of nitrosative damage and inflammation are similar in patients with incidentaloma, pheochromocytoma, and Cushing's or Conn's adenoma.
Adrenal tumors are associated with increased protein nitration/S-nitrosylation and inflammation.
肾上腺肿块是人类所有肿瘤中最常见的。亚硝化应激和炎症在癌症发展中的作用已得到证实。然而，它们是否参与肾上腺肿瘤的发病机制尚不清楚。本研究的目的是调查75例不同类型肾上腺肿块（无功能偶发瘤、嗜铬细胞瘤和库欣/原发性醛固酮增多症腺瘤）患者中亚硝化应激、炎症和缺氧诱导因子（HIF-1α）之间的相互作用。
采用分光光度法测定血浆中总一氧化氮（NO）、S-亚硝基硫醇、过氧亚硝酸盐硝基酪氨酸的浓度以及血清髓过氧化物酶（MPO）的活性，而白细胞介素1β（IL-1β）、肿瘤坏死因子α（TNF-α）和缺氧诱导因子1α（HIF-1α）的浓度则使用商用ELISA试剂盒进行测定。对照组由50名年龄和性别与研究组匹配的健康人组成。根据我们之前的实验预先确定受试者数量（检验效能=0.9；α=0.05）。
我们发现肾上腺肿瘤患者血浆中的亚硝化应激显著升高（一氧化氮升高、过氧亚硝酸盐升高、S-亚硝基硫醇升高和硝基酪氨酸升高），同时伴有炎症（髓过氧化物酶升高、白细胞介素1β升高和肿瘤坏死因子α升高）和缺氧（HIF-1α）生物标志物增加。过氧亚硝酸盐和硝基酪氨酸与醛固酮水平呈正相关。亚硝化应激也与炎症和HIF-1α相关。有趣的是，血浆硝基酪氨酸和血清MPO能够以高灵敏度和特异性区分肾上腺肿瘤患者与健康个体。此外，通过多变量回归分析，我们发现过氧亚硝酸盐和IL-1β依赖于皮质醇水平，而过氧亚硝酸盐、硝基酪氨酸和HIF-1α与醛固酮相关。遗憾的是，所评估的生物标志物均无法区分所研究的肿瘤类型，这表明偶发瘤、嗜铬细胞瘤以及库欣或原发性醛固酮增多症腺瘤患者的亚硝化损伤和炎症严重程度相似。
肾上腺肿瘤与蛋白质硝化/S-亚硝基化增加和炎症相关。
