结直肠癌中SIRT5的表达与18F-FDG PET/CT标准化摄取值的关系及机制研究
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南京医科大学附属南京医院(南京市第一医院)核医学科

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国家自然科学基金项目(青年项目,82001865);江苏省自然科学基金项目 (青年项目,BK20200145);南京医科大学临床科研课题(NMUB2019169)


Relationship between SIRT5 expression and 18F-FDG PET/CT standardized uptake in colorectal cancer and its mechanism study
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    摘要:

    目的:检测结肠癌中沉默调节蛋白5 (Sirtuin 5, SIRT5)表达情况并探讨其与18氟-脱氧葡萄糖(18F-fluorodeoxyglucose, 18F-FDG)最大标准化摄取值(the maximum standardized uptake value, SUVmax)、葡萄糖转运蛋白1(glucose trans porter-1,GLUT1)表达以及患者临床参数的关系。方法:回顾性分析78例术前行18F-FDG正电子发射型计算机断层扫描(positron emission tomography/computed tomography, PET/CT)结直肠癌患者,免疫组化分析SIRT5、GLUT1 蛋白表达,与SUVmax、临床参数、预后指标做相关分析。使用CRISPR/Cas9技术敲除SIRT5,研究其对结直肠癌细胞糖酵解以及缺氧诱导因子1α (hypoxia-inducible factor 1-alpha, HIF1α)转录活性的影响。结果:SIRT5在结直肠癌肿瘤组织中较癌旁组织高表达(p<0.01),且高表达者预后欠佳(p<0.01)。结直肠癌低分化者SUVmax表达和SIRT5明显高于中高分化者(12.72±2.60 v.s 18.18±4.06, p<0.01; 1.10±0.77 v.s 2.14±0.74, p<0.01)。结直肠癌患者SIRT5表达与SUVmax(Spearman相关系数= 0.648, p<0.05))呈正相关。敲除SIRT5基因,抑制肿瘤细胞18F-FDG、GLUT1表达和HIF1α转录活性。结论:SIRT5可通过HIF1α/GLUT1促进结直肠癌18F-FDG的摄取。SIRT5可能是结肠癌治疗的潜在靶点。

    Abstract:

    Objective:To determine whether fructose Sirtuin 5 ( SIRT5) expression is associated with fluorine 18 (18F) fluorodeoxyglucose (FDG) accumulation, glucose transporter 1(GLUTI) expression and clinical parameters in patients with colorectal cancer (CRC). Methods: Seventy-eight patients with CRC underwent 18F-FDG combined positron emission tomography and computed tomography (PET/CT). The relationship between maximum standardized uptake (SUVmax) and expression of SIRT5, glucose transporter 1 (GLUT1) immunohistochemical analysis, and the clinical prognosis were analyzed. The effects of SIRT5 on glycolysis and HIF1α transcriptional activity in colorectal cancer cells were investigated by using CRISPR/Cas9 technique?to Knock-out SIRT5. Results: The expression of SIRT5 was higher in CRC tissues when compared with in para-carcinoma?tissues. The prognosis was poor in patients with high SIRT5 expression. SUVmax and SIRT5 expression were higher in patients with poorly differentiated CRC (12.72±2.60 v.s 18.18±4.06, p<0.01; 1.10±0.77 v.s 2.14±0.74, p<0.01) than in those with well to moderately differentiated CRC. There was a positive relationship between SIRT5 expression and SUVmax (Spearman correlation coefficient = 0.648, p<0.05). Konck-out SIRT5 gene in CRC cells led to a significant decrease in GLUT1 expression, 18F-FDG uptake, and HIF1α transcriptional activity. Conclusion: SIRT5 might inhibit 18F-FDG uptake via the HIF1α/GLUT1 pathway in CRC. SIRT5 might be a potential target for the treatment of CRC.

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  • 收稿日期:2021-06-03
  • 最后修改日期:2021-08-03
  • 录用日期:2022-03-11
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