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DARS2 过表达与 PET/CT 代谢参数相关,并影响肺腺癌的糖酵解活性。

DARS2 overexpression is associated with PET/CT metabolic parameters and affects glycolytic activity in lung adenocarcinoma.

机构信息

Department of Nuclear Medicine, Hubei Provincial Clinical Research Center for Umbilical Cord Blood Hematopoietic Stem Cells, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, China.

Department of Pathology, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, China.

出版信息

J Transl Med. 2023 Aug 26;21(1):574. doi: 10.1186/s12967-023-04454-3.

Abstract

BACKGROUND

This study investigated the correlation between the expression of DARS2 and metabolic parameters of F-FDG PET/CT, and explored the potential mechanisms of DARS2 affecting the proliferation and glycolysis of lung adenocarcinoma (LUAD) cells.

METHODS

This study used genomics and proteomics to analyze the difference in DARS2 expression between LUAD samples and control samples. An analysis of 62 patients with LUAD who underwent F-FDG PET/CT examinations before surgery was conducted retrospectively. The correlation between DARS2 expression and PET/CT metabolic parameters, including SUVmax, SUVmean, MTV, and TLG, was examined by Spearman correlation analysis. In addition, the molecular mechanism of interfering with DARS2 expression in inhibiting LUAD cell proliferation and glycolysis was analyzed through in vitro cell experiments.

RESULTS

DARS2 expression was significantly higher in LUAD samples than in control samples (p < 0.001). DARS2 has high specificity (98.4%) and sensitivity (95.2%) in the diagnosis of LUAD. DARS2 expression was positively correlated with SUVmax, SUVmean, and TLG (p < 0.001). At the same time, the sensitivity and specificity of SUVmax in predicting DARS2 overexpression in LUAD were 88.9% and 65.9%, respectively. In vitro cell experiments have shown that interfering with DARS2 expression can inhibit the proliferation and migration of LUAD cells, promote cell apoptosis, and inhibit the glycolytic activity of tumor cells by inhibiting the expression of glycolytic related genes SLC2A1, GPI, ALDOA, and PGAM1.

CONCLUSIONS

Overexpression of DARS2 is associated with metabolic parameters on F-FDG PET/CT, which can improve LUAD diagnosis accuracy. DARS2 may be a useful biomarker to diagnose, prognosis, and target treatment of LUAD patients.

摘要

背景

本研究旨在探讨 DARS2 表达与 F-FDG PET/CT 代谢参数之间的相关性,并探索 DARS2 影响肺腺癌(LUAD)细胞增殖和糖酵解的潜在机制。

方法

本研究采用基因组学和蛋白质组学方法分析 LUAD 样本与对照样本之间 DARS2 表达的差异。回顾性分析了 62 例接受 F-FDG PET/CT 检查的 LUAD 患者的资料,分析 DARS2 表达与 PET/CT 代谢参数(SUVmax、SUVmean、MTV 和 TLG)之间的相关性,采用 Spearman 相关分析进行检验。此外,通过体外细胞实验分析干扰 DARS2 表达抑制 LUAD 细胞增殖和糖酵解的分子机制。

结果

与对照样本相比,LUAD 样本中 DARS2 的表达显著升高(p<0.001)。DARS2 对 LUAD 的诊断具有较高的特异性(98.4%)和敏感性(95.2%)。DARS2 表达与 SUVmax、SUVmean 和 TLG 呈正相关(p<0.001)。同时,SUVmax 预测 LUAD 中 DARS2 过表达的敏感性和特异性分别为 88.9%和 65.9%。体外细胞实验表明,干扰 DARS2 表达可抑制 LUAD 细胞的增殖和迁移,促进细胞凋亡,并通过抑制糖酵解相关基因 SLC2A1、GPI、ALDOA 和 PGAM1 的表达,抑制肿瘤细胞的糖酵解活性。

结论

DARS2 过表达与 F-FDG PET/CT 代谢参数相关,可提高 LUAD 诊断的准确性。DARS2 可能是诊断、预后和 LUAD 患者靶向治疗的有用生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad89/10463715/858645412543/12967_2023_4454_Fig1_HTML.jpg

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