肿瘤组织的代谢组学分析揭示了并发糖尿病的非小细胞肺癌患者的代谢变化。
Metabolomic Profiling of Tumor Tissues Unveils Metabolic Shifts in Non-Small Cell Lung Cancer Patients with Concurrent Diabetes Mellitus.
发表日期:2024 Aug 20
作者:
Xiaohong Lyu, Yujue Wang, Yuan Xu, Zhewei Zhao, Hongsheng Liu, Zeping Hu
来源:
JOURNAL OF PROTEOME RESEARCH
摘要:
目前仍缺乏对2型糖尿病(T2DM)对非小细胞肺癌(NSCLC)代谢状态的确切影响的全面了解。本研究探讨了 NSCLC 和 T2DM 共存患者与 NSCLC 患者相比肿瘤组织的代谢变化。采用临床分析和代谢组学相结合的方法,包括 20 名 NSCLC 患者和 20 名 NSCLC T2DM 患者。使用液相色谱-质谱(LC-MS)方法对肿瘤组织进行靶向代谢组学分析。在正交偏最小二乘判别分析 (OPLS-DA) 中,观察到 NSCLC T2DM 和匹配的 NSCLC 组织样本之间存在明显的分离。此外,还发现糖尿病/非糖尿病肿瘤组织样本中 7 种代谢物的水平存在显着差异。相关途径包括精氨酸生物合成、谷胱甘肽代谢、精氨酸和脯氨酸代谢、嘌呤代谢、生物素代谢和组氨酸代谢。 3-苯乳酸、肉碱-C5、肉碱-C12和血清素与NSCLC患者的空腹血糖水平呈正线性相关。尿苷、哌可酸、胞嘧啶和空腹血糖水平被发现呈负相关。我们的结果表明,与单纯 NSCLC 患者相比,并发 T2DM 的 NSCLC 患者的肿瘤组织表现出明显的代谢变化。
A comprehensive understanding of the exact influence of type 2 diabetes mellitus (T2DM) on the metabolic status of non-small cell lung cancer (NSCLC) is still lacking. This study explores metabolic alterations in tumor tissues among patients with coexisting NSCLC and T2DM in comparison with NSCLC patients. A combined approach of clinical analysis and metabolomics was employed, including 20 NSCLC patients and 20 NSCLC+T2DM patients. Targeted metabolomics analysis was performed on tumor tissues using the liquid chromatography-mass spectrometry (LC-MS) approach. A clear segregation was observed between NSCLC+T2DM and matched NSCLC tissue samples in Orthogonal Partial Least Squares Discrimination Analysis (OPLS-DA). Furthermore, the levels of 7 metabolites are found to be significantly different between diabetes/nondiabetes tumor tissue samples. The related pathways included arginine biosynthesis, glutathione metabolism, arginine and proline metabolism, purine metabolism, biotin metabolism, and histidine metabolism. 3-Phenyllactic acid, carnitine-C5, carnitine-C12, and serotonin showed a positive linear correlation with fasting blood glucose levels in NSCLC patients. Uridine, pipecolic acid, cytosine, and fasting blood glucose levels were found to have a negative correlation. Our results suggest that NSCLC patients with concurrent T2DM exhibit distinct metabolic shifts in tumor tissues compared to those of solely NSCLC patients.