Research Institute of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, People's Republic of China.
Department of Cardiothoracic Surgery, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Med Oncol. 2020 Nov 16;37(12):113. doi: 10.1007/s12032-020-01439-w.
The incidence of gastric cancer cachexia is high and the clinical management is poor, so the study aimed to clarify the mechanism of muscle wasting to better screen patients with gastric cancer cachexia. Gastric cancer patients undergoing radical gastrectomy were divided into cachexia with sarcopenia (CS, n = 13) and normal (N, n = 10) two groups. The possible mechanism of skeletal muscle reduction was explored through Tandem Mass Tag (TMT) technique, Perls staining, Western blot analysis and measurement of oxidative stress indicators. The preoperative weight, weight loss, body mass index, calorie intake and skeletal muscle index values of the CS group were significantly lower than those of the N group (P < 0.05). We identified 114 differentially expressed proteins (DEP) in the muscles of two groups using TMT analysis. Bioinformatics analysis of DEP revealed that ferritin, iron and oxidative stress may be related to skeletal muscle consumption. Following Perls staining and measurement iron concentration in skeletal muscles, we found that the iron in the muscles of the CS group was significantly increased, and at the same time, western blot analysis showed that the expression of ferritin in the CS group was significantly increased and regulated by hepcidin-ferroportin axis. Finally, the CS group showed increased oxidative stress and weakened antioxidant stress systems in the muscles compared with the N group when oxidative stress indicators were analyzed. In conclusion, iron overload may be related to muscle loss in patients with gastric cancer cachexia. Gastric cancer patients with elevated ferritin are more likely to have muscle wasting.
胃癌恶病质的发病率高，临床管理效果差，因此本研究旨在阐明肌肉减少的机制，以便更好地筛选出患有胃癌恶病质的患者。接受根治性胃切除术的胃癌患者被分为伴有恶病质的肌少症（CS，n = 13）和正常（N，n = 10）两组。通过串联质量标签（TMT）技术、普鲁士蓝染色、Western blot 分析和氧化应激指标测量，探讨了骨骼肌减少的可能机制。CS 组的术前体重、体重减轻、体重指数、热量摄入和骨骼肌指数值明显低于 N 组（P < 0.05）。使用 TMT 分析在两组肌肉中鉴定出 114 个差异表达蛋白（DEP）。对 DEP 的生物信息学分析表明，铁蛋白、铁和氧化应激可能与骨骼肌消耗有关。普鲁士蓝染色和测量骨骼肌铁浓度后，我们发现 CS 组肌肉中的铁明显增加，同时 Western blot 分析显示 CS 组铁蛋白的表达明显增加，并受铁调素-亚铁转运蛋白轴的调节。最后，与 N 组相比，CS 组肌肉中的氧化应激标志物增加，抗氧化应激系统减弱。综上所述，铁过载可能与胃癌恶病质患者的肌肉减少有关。铁蛋白升高的胃癌患者更有可能出现肌肉减少。
