Abstract
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.
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Funding
This study was supported by National Natural Science Foundation of China (Grant No. 81770531) and Jiangsu Outstanding Youth Foundation (Grant No. BK20170009).
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WXY and ZY designed the study. GM, WSL, GXJ, and ZL collected the samples. ZD performed the experiments. ZD and ZY analyzed the data and wrote the manuscript. WXY and LGL reviewed/edited the manuscript. WXY and LGL supervised the research. All authors read and approved the final manuscript.
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The study was approved by the Ethics Committee of the Jinling hospital (Approval No. 2017NZKY-003-01).
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Zhou, D., Zhang, Y., Mamtawla, G. et al. Iron overload is related to muscle wasting in patients with cachexia of gastric cancer: using quantitative proteome analysis. Med Oncol 37, 113 (2020). https://doi.org/10.1007/s12032-020-01439-w
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DOI: https://doi.org/10.1007/s12032-020-01439-w