| Gastric cancer is one of the most common malignant tumors in China.Advanced gastric cancer patients are more likely to develop cancer cachexia and have a poor prognosis.Cancer cachexia is characterized by skeletal muscle reduction(sarcopenia),so it is of great significance to explore the mechanism of skeletal muscle loss in cachexia for the treatment of cancer cachexia.For this purpose,this study was divided into two parts.The first part was to study the value of human body composition analysis,such as gastric cancer skeletal muscle reduction,to predict the long-term clinical outcome in patients with radical gastrectomy,so as to provide an effective basis for clinical diagnosis and mechanism research.In the second part,molecular biology methods such as Tandem Mass Tags(TMT)were used to analyze the pathogenesis and regulatory mechanism of gastric cancer cachexia from an overall perspective.The results of this study will further strengthen the theoretical basis of cachexia with sarcopenia in gastric cancer,and provide a basis and new thinking for clinical treatment.Part1 The value of human body composition analysis such as gastric cancer skeletal muscle reduction in predicting long-term clinical outcome Objective:The purpose of this study was to assess the body composition score(BCS)impact on 3-year survival after radical gastrectomy in patients with gastric cancer.Methods:Clinical data of gastric cancer patients in our department from September 2015 to June 2017 were collected.The patients were divided into three groups:BCSO(having normal skeletal muscle or adipose mass),BCS1(having low skeletal muscle mass only),and BCS2(having low skeletal muscle and adipose mass)according to their third lumbar vertebra skeletal muscle index and fat index calculated using abdominal computed tomography images.The clinicopathological indicators,postoperative complications,3-year over survival(OS)rate after radical gastrectomy,and cause of death among the three groups were compared.Results:A total of 187 patients were enrolled in the study,in which 102 patients(54.6%)had BCSO,76(40.6%)had BCS1 and 9(4.8%)had BCS2,Although BCS was positively correlated with postoperative complications,there was no significant difference in postoperative complications among the three groups.3-year OS was significantly shortened with each 1-score increase in BCS(Log-rank P<0.001),the main cause of death was cancer-related.Multivariate Cox regression analyses showed that no neoadjuvant chemotherapy,tumor stage ?,BCS1,and BCS2 were independent prognostic factors for 3-year OS after radical gastrectomy.Conclusion:We demonstrated that analysis of human body composition such as gastric cancer skeletal muscle reduction has the value of predicting the long-term clinical outcome.Part2 The mechanism of cachexia with sarcopenia in gastric cancer Objective:The probability of cancer cachexia in patients with gastric cancer is high,and it is important to clarify the mechanism of muscle wasting to improve the prognosis of patients.Methods:Patients undergoing radical gastrectomy for gastric cancer were divided into cachexia with sarcopenia(CS)and normal(N)two groups,and the abdominal muscles were collected during the operation.The possible mechanism of skeletal muscle reduction was explored through the molecular biological differences between the two groups using TMT technique,Perls stain,Western blot analysis,and measurement of oxidative stress indicators.Results:The preoperative weight,weight loss,BMI 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 in the muscles of the CS group and N group using TMT and Liquid Chromatography-Mass Spectrometry analysis.Bioinformatics analysis revealed that ferritin,iron,and oxidative stress may be related to sarcopenia.Following Perls stain,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(iron deposits)in the CS group was significantly increased.Finally,when oxidative stress indicators in the muscles of the two groups were analyzed,the CS group showed increased oxidative stress and weakened antioxidant stress systems in the muscles compared with the N group.Conclusions:Iron overload is associated with muscle loss in patients with gastric cancer. |
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