出 处:《中华实验外科杂志》2024年第10期2360-2363,共4页Chinese Journal of Experimental Surgery
基 金:河南省医学科技攻关计划项目(LHGJ20210792)。
摘 要:目的:探讨骨肉瘤组织糖酵解关键酶和代谢物变化及其意义。方法:选取2021年6月至2023年12月郑州市骨科医院收治的56例骨肉瘤组织和癌旁组织作为研究对象,采用蛋白质组学分析骨肉瘤和癌旁组织差异表达蛋白;分析糖酵解通路蛋白表达变化;采用蛋白质免疫印迹分析糖酵解相关酶的表达水平;采用质谱法检测肿瘤组织和癌旁组织6-磷酸葡萄糖、甘油醛3-磷酸、烯醇式丙酮酸、丙酮酸和乳酸水平。组间计量数据比较采用t检验。结果:采用蛋白质组学技术鉴定差异表达蛋白1596个个,其中上调蛋白1044个个,下调蛋白542个。通路富集分析显示包括糖酵解通路、氧化磷酸化、脂肪酸代谢、蛋白质翻译、DNA损伤修复和细胞信号转导等通路中。糖酵解通路多个蛋白表达上调,分别为己糖激酶、6-磷酸果糖激酶、丙酮酸激酶、醛缩酶和乳酸脱氢酶A。癌旁组织中己糖激酶、6-磷酸果糖激酶、醛缩酶、丙酮酸激酶和乳酸脱氢酶A表达水平(0.75±0.12、0.82±0.26、0.70±0.11、0.76±0.08、0.64±0.09)明显低于骨肉瘤组织表达水平(1.29±0.12、1.55±0.19、1.34±0.14、1.27±0.21、1.18±0.12),差异有统计学意义(t=10.840、7.866、12.610、7.840、12.450,P<0.05)。癌旁组织中6-磷酸葡萄糖、甘油醛3-磷酸、烯醇式丙酮酸、丙酮酸和乳酸水平[(7.62±0.66)、(6.38±0.99)、(5.90±0.63)、(6.76±0.86)、(5.43±0.80)mmol/mg]明显低于骨肉瘤组织表达水平[(11.80±1.39)、(7.63±0.70)、(9.05±0.92)、(8.81±0.93)、(9.68±0.87)mmol/mg],差异有统计学意义(t=9.408、3.540、9.797、5.539、12.420,P<0.05)。结论:骨肉瘤组织中糖酵解相关酶活性表达水平显著增加,烯醇式丙酮酸和乳酸水平显著升高,促进了肿瘤细胞的进展。Objective:To investigate the changes and significance of key glycolysis enzymes and metabolites in osteosarcoma.Methods:56 cases of osteosarcoma and adjacent tissues admitted to Zhengzhou Orthopedic Hospital from June 2021 to December 2023 were selected as the study objects,and proteomics was used to analyze the differentially expressed proteins of osteosarcoma and adjacent tissues.The expression of glycolytic pathway protein was analyzed.The expression levels of glycolytic-related enzymes were analyzed by Western blotting.The levels of glucose 6-phosphate,glyceraldehyde 3-phosphate,phosphoenolpyruvate,pyruvate and lactic acid in tumor tissues and adjacent tissues were detected by mass spectrometry.T test was used to compare measurement data between groups.Results:1596 differentially expressed proteins were identified by proteomics,including 1044 up-regulated proteins and 542 down-regulated proteins.Pathway enrichment analysis showed that glycolysis pathway,oxidative phosphorylation,fatty acid metabolism,protein translation,DNA damage repair and cell signal transduction were involved.Several proteins in glycolytic pathway were up-regulated,including hexokinase,6-phosphofructokinase,pyruvate kinase,aldolase and lactate dehydrogenase A.The expression levels of hexokinase,6-phosphofructokinase,aldolase,pyruvate kinase and lactate dehydrogenase A in adjacent tissues(0.75±0.12,0.82±0.26,0.70±0.11,0.76±0.08,0.64±0.09) was significantly lower than that of osteosarcoma tissue(1.29±0.12,1.55±0.19,1.34±0.14,1.27±0.21,1.18±0.12),the difference was statistically significant(t=10.840,7.866,12.610,7.840,12.450,P<0.05).The levels of glucose 6-phosphate,glyceraldehyde 3-phosphate,phosphoenolpyruvate,pyruvate and lactic acid in adjacent tissues[(7.62±0.66),(6.38±0.99),(5.90±0.63),(6.76±0.86),(5.43±0.80)mmol/mg]were significantly lower than the osteosarcoma tissue expression level[(11.80±1.39),(7.63±0.70),(9.05±0.92),(8.81±0.93),(9.68±0.87)mmol/mg],the difference was statistically significant(t=9.408,3.540,9.79
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