结直肠癌中SIRT5的表达与^(18)F-FDG PET/CT标准化摄取值的关系及机制研究

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

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(;F-fluorodeoxyglucose,^(18)F-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;F-FDG正电子发射型计算机断层扫描(positron emission tomography/computed tomography,PET/CT)的结直肠癌患者,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:结直肠癌肿瘤组织中SIRT5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和SIRT5表达明显高于中高分化者(18.18±4.06 vs. 12.72±2.60,P <0.01;2.14±0.74 vs. 1.10±0.77,P <0.01)。结直肠癌患者SIRT5表达与SUVmax呈正相关(Spearman相关系数=0.648,P <0.05)。敲除SIRT5基因,抑制肿瘤细胞^(18)F-FDG摄取、GLUT1表达和HIF1α转录活性。结论:SIRT5可通过HIF1α/GLUT1促进结直肠癌^(18)F-FDG的摄取,SIRT5可能是结肠癌治疗的潜在靶点。

Objective:This study aims to determine whether fructose Sirtuin 5(SIRT5)expression is associated with fluorine 18(;F)fluorodeoxyglucose(FDG)accumulation,glucose transporter 1(GLUTI)expression and clinical parameters in patients with colorectal cancer(CRC). Methods:Seventy-eight patients with CRC underwent ^(18)F-FDG combined positron emission tomography and computed tomography(PET/CT)were analyzed. The relationship between maximum standardized uptake(SUVmax)and expression of SIRT5 and GLUT1 was analyzed,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(P < 0.01). The prognosis was poor in patients with high SIRT5 expression(P < 0.01). SUVmax and SIRT5 expression were higher in patients with poorly differentiated CRC than in those with well to moderately differentiated CRC(18.18±4.06 vs. 12.72±2.60,P < 0.01;2.14±0.74 vs. 1.10±0.77,P < 0.01). 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,^(18)F-FDG uptake,and HIF1α transcriptional activity. Conclusion:SIRT5 might inhibit ^(18)F-FDG uptake via the HIF1α/GLUT1 pathway in CRC. SIRT5 might be a potential target for the treatment of CRC.