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SFXN1 作为 LUAD 的潜在诊断和预后生物标志物与 F-FDG 代谢参数相关。

SFXN1 as a potential diagnostic and prognostic biomarker of LUAD is associated with F-FDG metabolic parameters.

机构信息

Department of Nuclear Medicine and Institute of Anesthesiology and Pain, Hubei Provincial Clinical Research Center for Precision Diagnosis and Treatment of Liver Cancer, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China.

Department of Nuclear Medicine and Institute of Anesthesiology and Pain, Hubei Provincial Clinical Research Center for Precision Diagnosis and Treatment of Liver Cancer, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China; Hubei Provincial Clinical Research Center for Umbilical Cord Blood Hematopoietic Stem Cells, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China; Hubei Key Laboratory of Embryonic Stem Cell Research, Shiyan 442000, Hubei, China.

出版信息

Lung Cancer. 2024 Feb;188:107449. doi: 10.1016/j.lungcan.2023.107449. Epub 2023 Dec 27.

Abstract

BACKGROUND

Sideroflexin 1 (SFXN1) has been discovered as a novel tumor marker for lung adenocarcinoma, but data on its importance in the development of lung adenocarcinoma is still limited. This study evaluated the correlation between SFXN1 and parameters related to F-flurodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT), and further explored the role of SFXN1 in the value-added and glycolytic processes of LUAD.

METHOD

The expression and prognostic value of SFXN1 mRNA in LUAD were analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data base. Retrospective analysis of F-FDG PET imaging and metabolic parameters in 42 patients to explore the relationship between the expression of SFXN1 and glucose metabolism levels in lung adenocarcinoma and its clinical significance. H1975 cells were selected as the in vitro research object, and the biological effects of SFXN1 on LUAD were further elucidated through Edu proliferation assay, CCK8 activity assay, wound healing experiment, and cell flow cytometry.

RESULT

SFXN1 is highly expressed in various tumors, including LUAD, and its high expression can serve as an independent predictor of overall survival in lung adenocarcinoma. In addition, the expression of SFXN1 in LUAD was significantly correlated with F-FDG PET/CT parameters: maximum and average standardized uptake values (SUVmax and SUVmean), as well as total lesion glycolysis (TLG) (rho = 0.574, 0.589, and 0.338, p < 0.05), which can predict the expression of SFXN1 with an accuracy of 0.934. In vitro functional experiments have shown that knocking down SFXN1 inhibits the proliferation and migration of LUAD cells, promotes cell apoptosis, and may inhibit tumor activity by regulating the expression of glycolytic related genes SLC2A1, HK2, GPI, ALDOA, GAPDH, ENO1, PKM, and LDHA.

CONCLUSION

The overexpression of SFXN1 is closely related to FDG uptake, and SFXN1, as a promising prognostic biomarker, may mediate the development of LUAD through the glycolytic pathway.

摘要

背景

Sideroflexin 1(SFXN1)已被发现为肺腺癌的新型肿瘤标志物,但有关其在肺腺癌发展中的重要性的数据仍然有限。本研究评估了 SFXN1 与 F-氟脱氧葡萄糖(F-FDG)正电子发射断层扫描/计算机断层扫描(PET/CT)相关参数之间的相关性,并进一步探讨了 SFXN1 在 LUAD 增值和糖酵解过程中的作用。

方法

使用癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)数据库分析 SFXN1 mRNA 在 LUAD 中的表达和预后价值。对 42 例患者的 F-FDG PET 成像和代谢参数进行回顾性分析,以探讨 SFXN1 在肺腺癌中的表达与葡萄糖代谢水平之间的关系及其临床意义。选择 H1975 细胞作为体外研究对象,通过 Edu 增殖试验、CCK8 活性测定、划痕愈合实验和细胞流式细胞术进一步阐明 SFXN1 对 LUAD 的生物学作用。

结果

SFXN1 在包括 LUAD 在内的各种肿瘤中高表达,其高表达可作为肺腺癌总生存期的独立预测因子。此外,SFXN1 在 LUAD 中的表达与 F-FDG PET/CT 参数显著相关:最大和平均标准化摄取值(SUVmax 和 SUVmean)以及总病变糖酵解(TLG)(rho=0.574、0.589 和 0.338,p<0.05),可预测 SFXN1 的表达,准确率为 0.934。体外功能实验表明,敲低 SFXN1 可抑制 LUAD 细胞的增殖和迁移,促进细胞凋亡,并可能通过调节糖酵解相关基因 SLC2A1、HK2、GPI、ALDOA、GAPDH、ENO1、PKM 和 LDHA 的表达来抑制肿瘤活性。

结论

SFXN1 的过表达与 FDG 摄取密切相关,SFXN1 作为一种有前途的预后生物标志物,可能通过糖酵解途径介导 LUAD 的发生发展。

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