文章摘要
苹果酸-天冬氨酸穿梭关键酶和肺腺癌临床特征的关联*
Investigation association between key enzymes in malate-aspartic acid shuttle and clinical features of lung adenocarcinoma*
投稿时间:2019-01-26  修订日期:2019-01-31
DOI:
中文关键词: 有氧糖酵解  苹果酸-天冬氨酸穿梭  肺腺癌  生存分析  天冬氨酸氨基转移酶2
英文关键词: Aerobic glycolysis  Malic acid-aspartate shuttle  Lung adenocarcinoma  Survival analysis  Aspartate aminotransferase 2
基金项目:国家自然科学基金项目(面上项目,重点项目,重大项目)
作者单位E-mail
辛向兵 空军军医大学唐都医院胸腔外科 陕西 西安 中国 429392090@qq.com 
熊延路 空军军医大学唐都医院胸腔外科 陕西 西安 中国  
思越 空军军医大学基础医学院学员队 陕西 西安 中国  
潘明宏 空军军医大学基础医学院学员队 陕西 西安 中国 空军军医大学唐都医院胸腔外科 陕西 西安 中国  
石明延 空军军医大学基础医学院学员队 陕西 西安 中国
空军军医大学唐都医院胸腔外科 陕西 西安 中国 
 
卢强 空军军医大学唐都医院胸腔外科 陕西 西安 中国  
李小飞 空军军医大学唐都医院胸腔外科 陕西 西安 中国  
韩勇 空军军医大学唐都医院胸腔外科 陕西 西安 中国 hanyong_td@163.com 
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中文摘要:
      目的:有氧糖酵解是肿瘤的重要代谢特征,和肿瘤的恶性进展密切相关。苹果酸-天冬氨酸穿梭是维持有氧糖酵解运转的重要代谢进程,其在肿瘤中尤其是肺腺癌中的作用尚缺乏充分的研究。本研究探索了苹果酸-天冬氨酸穿梭途径中的关键酶和肺腺癌临床特征的关联。方法:我们首先从GEO数据库、TCGA平台中获取了肺腺癌的转录组数据和相应的临床信息;苹果酸脱氢酶1/2和天冬氨酸氨基转移酶1/2是该途径中的关键酶,我们通过非参数检验分别分析了这四种关键酶在肿瘤组织和正常组织之间的表达差别;接着我们分析了这些关键酶和肺腺癌总生存期之间的关系;最后我们探讨了生存相关的关键酶和肺腺癌人口学特征、TNM参数以及肿瘤恶性生物学标志物之间的关系。结果:我们发现在肺腺癌中,这四种关键酶大部分都高表达;而生存分析发现只有天冬氨酸氨基转移酶2 (glutamic-oxaloacetic transaminase 2, GOT2)和肺腺癌的生存概率有关,高表达GOT2的病人往往具有较短的总生存期;但是GOT2和肺腺癌的人口学特征、TNM参数、临床分期无明显统计学关联;最后我们发现GOT2和肿瘤恶性标志物PCNA呈正相关。结论:本研究表明苹果酸-天冬氨酸穿梭途径中关键酶GOT2和肺腺癌恶性进展有关,为探索肺腺癌发病机制以及研究防治策略提供一定启示。
英文摘要:
      Objective:Aerobic glycolysis, a key metabolic feature of tumors, plays an important role in malignant progression. The malate-aspartate shuttle sustains aerobic glycolysis heavily, but its role in tumor, especially in lung adenocarcinoma, is still lack of sufficient investigation. This research explored the association between key enzymes in the malate-aspartate shuttle pathway and clinical features of lung adenocarcinoma. Methods:We first obtained transcriptome data and corresponding clinical annotation of lung adenocarcinoma from GEO database and TCGA platform; Malate dehydrogenase 1/2 and glutamic-oxaloacetic transaminase 1/2 are key enzymes in malate-aspartate shuttle. We analyzed the differential expression of these four key enzymes between tumor tissue and normal tissue by non-parametric test; We then analyzed the relationship between these key enzymes and the overall survival of lung adenocarcinoma; Finally we explored relationship between survival-related key enzymes and clinical features of lung adenocarcinoma like demographic characteristics, TNM parameters, and tumor malignant biomarkers. Results: We found that most of these four key enzymes were highly expressed in lung adenocarcinoma; Survival analysis showed that only glutamic-oxaloacetic transaminase 2 (GOT2) was associated with survival probability of lung adenocarcinoma, and patients with high expression of GOT2 often had shorter overall survival time; However, there was no statistically significant association between GOT2 and clinical characters like demographic characteristics, TNM parameters, and clinical stage of lung adenocarcinoma. Finally, we found that GOT2 was positively correlated with the tumor malignant marker PCNA. Conclusion:This study indicated that the key enzyme GOT2 in the malate-aspartate shuttle pathway was associated with the malignant progression of lung adenocarcinoma, which provides implications for exploring the pathogenesis of lung adenocarcinoma and its coping approaches.
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