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第42卷第3期                           南京医科大学学报(自然科学版)
                  2022年3月                   Journal of Nanjing Medical University(Natural Sciences)     ·333 ·


               ·基础研究·

                结直肠癌中SIRT5的表达与 F⁃FDG PET/CT标准化摄取值的关
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                系及机制研究



                施   良 ,尤琴琴 ,沙       鑫 ,安淑娴 ,刘建军 ,王           峰  1*
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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,江苏                        南京    210006;江苏大学附属医院普外科,江苏             镇江
                1                                                               2
                212001;上海交通大学附属仁济医院核医学科,上海                200127
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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 氟⁃脱氧葡萄糖( F⁃fluorodeoxyglucose,
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                 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,
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                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 emis⁃
                sion 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⁃in⁃
                ducible 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
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                SIRT5基因,抑制肿瘤细胞 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 F⁃
                FDG的摄取,SIRT5可能是结肠癌治疗的潜在靶点。
               [关键词] 结直肠癌;SIRT5;SUVmax;HIF1α
               [中图分类号] R735.3                   [文献标志码] A                       [文章编号] 1007⁃4368(2022)03⁃333⁃07
                doi:10.7655/NYDXBNS20220304


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

                        1           1        2           3          3           1*
                SHI Liang ,YOU Qinqin ,SHA Xin ,AN Shuxian ,LIU Jianjun ,WANG Feng
                1 Department of Nuclear Medicine,the Affiliated Nanjing Hospital of Nanjing Medical University(Nanjing First
                Hospital),Nanjing 210006;Department of General Surgery,the Affiliated Hospital of Jiangsu University,Zhenjiang
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                212001;Department of Nuclear Medicine,Ren Ji Hospital Affiliated to Shanghai Jiao Tong University,Shanghai
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                200127,China


               [Abstract] Objective:This study aims to determine whether fructose Sirtuin 5(SIRT5)expression is associated with fluorine 18( F)
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                fluorodeoxyglucose(FDG)accumulation,glucose transporter 1(GLUTI)expression and clinical parameters in patients with colorectal
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                cancer(CRC). Methods:Seventy⁃eight patients with CRC underwent 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

               [基金项目] 国家自然科学基金(82001865);江苏省自然科学基金(BK20200145);南京医科大学临床科研课题(NMUB
                2019169)
                ∗
                通信作者(Corresponding author),E⁃mail:fengwangcn@hotmail.com
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