胃癌住院患者营养状况及恶液质生物标志物研究

Investigation and analysis of nutritional status of gastric cancer patients and study on biomarkers of cachexia

目的基于营养风险筛查2002(NRS 2002)量表对胃癌患者营养状况进行调查和分析,并基于高通量测序结果,筛选与恶液质相关外泌体标志物。方法选取2016年12月至2018年12月在空军军医大学第一附属医院住院接受胃癌根治术治疗患者1134例为研究对象。根据NRS 2002量表比较营养状况与人口学特征、疾病进展、实验室指标和结局的相关性。同时抽取恶液质患者(n=3)和非恶液质患者(n=2)外周血进行全转录基因组测序,筛选差异表达的外泌体mi RNA作为胃癌恶液质的预测标志物。结果1134例患者中营养不良患者共772例,占患者总人数的68.08%。营养不良的发病存在年龄、吸烟饮酒史、肿瘤分期、体质指数(BMI)、实验室指标和预后的差异:老年患者(≥60岁)营养不良发生率显著高于<60岁的非老年患者(P=0.007),吸烟(P<0.001)和饮酒(P=0.005)均对患者的营养状况产生明显影响,胃癌患者营养状况随肿瘤分期增高而不断恶化(P=0.018)。营养不良者白蛋白、血红蛋白和BMI均显著低于营养良好患者,而白细胞计数高于营养良好者。多因素Logistic回归分析结果显示,营养不良是胃癌患者预后不良的独立危险因素。此外,通过全基因组测序,血浆外泌体mi R-206被鉴定为恶液质早期诊断的生物标志物,以弥补恶液质早期诊断方法的不足。结论胃癌患者营养不良发生率较高,且胃癌患者营养状况与其年龄、吸烟饮酒史、肿瘤分期、BMI、实验室指标等因素有关,并且是胃癌患者预后不良的独立危险因素。此外本文鉴定了一种新的血浆外泌体生物标志物mi R-206,用于恶液质的早期诊断。

Objective The nutritional status of gastric cancer patients based on the nutritional risk screening scale(NRS 2002)were investigated and analyzed.Based on the results of high-throughput sequencing.the biomarker related to cachexia were screened.Method 1134 patients with gastric cancer who were hospitalized in the First ffiliated Hospital of Air Force Military Medical University from December 2016 to December 2018 were selected a the study subjects.The nutritional status of patients was evaluated acoording to the NRS 2002.The orrelation between nutritional status and demographic characteristics,disease progression,laboratory indicators and outcomes was comnpared.At the same time,the blood of patients with cachexia(n=3)and nom-cachexia(n=2)were extracted for full transcriptional genone sequencing.and the diferentially expresed miRNAs were screened a a predictive biomarker of cachexia in gastric cancer.Result 772 of the 1134 patients were malnourished and accounting for 68.08%of the total number of patients.The incidence of malnutrition has dfferences in age,smoking and drinking history,tunor stage,BMI,laboratory indicators and short-term adverse outcomes.The incidence of malutition in eldely patent(≥60 years old)was significantly higher than that in<60 years old non-elderly patients(P=0.007).Smoking(P<0.001)and drinking(P=0.005)have a sigificant impact on the nutritional status of patients with gastric cancer.The nutritional status of gastric cancer patients worsened with the increase of tumor stage(P=0.018).The albumin,hemoglobin and BMI of patients with malnutrition were signifcanly lower than those with good nutritinal status,while white blood cell count was higher.Multivariate Logistic regression analysis showed that malnutrition was an independent risk factor for poor prognosis in patients with gstric cancer.Furthemore,plasma exosomal miR-206 was identifed as a biomarker for the early diagnosis of cachexia via wbole-gene sequencing to make up for the lack of methods for the early diagnosis of cachexia.Conclusion The incidence of malnutrition in gstric cancer patients is high,and the nutritional status of gastric cancer patients is related to age,smoking and drinking history,tumor stage,BMI,laboratory indicators and other factors.Malnutnition is an independent risk factor for poor prognosis of gastric cancer patients.Furthermore,we identified a novel plasma exosomal biomarker,miR-206,for.the early diagnosis of cachexia.