小核核糖核蛋白D1在胃癌中的表达水平及对患者预后的影响  

Expression Level of Small Nuclear Ribonucleoprotein D1 in Gastric Cancer and Its Effect on Prognosis

作　　者：殷丽霞 杨晶晶 牛民主 耿志军 李江艳 李静 YIN Lixia;YANG Jingjing;NIU Minzhu;GENG Zhijun;LI Jiangyan;LI Jing(Department of Laboratory Medicine,The First Affiliated Hospital of Bengbu Medical University,Bengbu,Anhui 233000,China;Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-Related Diseases,The First Affiliated Hospital of Bengbu Medical University,Bengbu,Anhui 233000,China;College of Laboratory Medicine,Bengbu Medical University,Bengbu,Anhui 233000,China;Central Laboratory,The First Affiliated Hospital of Bengbu Medical University,Bengbu,Anhui 233000,China)

机构地区：[1]蚌埠医科大学第一附属医院检验科,安徽蚌埠233000 [2]蚌埠医科大学第一附属医院炎症相关性疾病基础与转化研究安徽省重点实验室,安徽蚌埠233000 [3]蚌埠医科大学检验医学院,安徽蚌埠233000 [4]蚌埠医科大学第一附属医院中心实验室,安徽蚌埠233000

出　　处：《中国医学科学院学报》2025年第1期1-9,共9页Acta Academiae Medicinae Sinicae

基　　金：安徽省高校协同创新项目(GXXT-2020-020);安徽省高校优秀青年基金(2022AH030138);安徽省卫生健康科研项目(AHWJ2022b088)。

摘　　要：目的探讨小核核糖核蛋白D1(SNRPD1)在胃癌组织中的表达情况,分析其表达水平对胃癌患者远期预后的预测价值及可能的作用机制。方法采用UALCAN和基因表达谱交互分析(GEPIA)数据库分析SNRPD1在泛癌中的表达水平及其与胃癌预后的关系。回顾性分析2014年1月至2017年1月蚌埠医科大学第一附属医院行胃癌根治术的109例患者的临床资料。收集胃癌和癌旁组织,采用免疫组织化学染色检测SNRPD1的表达。采用慢病毒转染技术构建SNRPD1稳定高表达和低表达的BGC-823胃癌细胞模型,采用CCK-8法和细胞克隆实验分析SNRPD1对胃癌细胞增殖的影响,流式细胞术分析细胞周期改变,免疫印记法检测信号通路。结果UALCAN和GEPIA数据库分析结果显示SNRPD1在胃癌(P<0.001)等多种恶性肿瘤组织中呈高表达;免疫组织化学染色结果显示SNRPD1在胃癌组织中的表达水平显著高于癌旁组织(P<0.001),且表达量与胃癌患者癌胚抗原(P<0.001)、糖类抗原19-9(P<0.001)、G分期(P=0.042)、T分期(P=0.002)和N分期(P=0.027)呈正相关。SNRPD1高表达对胃癌远期预后具有预测价值(P<0.001),是胃癌患者死亡的独立危险因素(P=0.003)。基因本体和京都基因与基因组百科全书富集分析结果显示,SNRPD1生物学功能可能与调控细胞周期有关。CCK-8法和细胞克隆实验结果显示,上调SNRPD1可显著促进胃癌细胞增殖(P<0.001,P<0.001);免疫印迹法分析结果显示,上调SNRPD1使细胞周期蛋白依赖性激酶6、G 1/S-特异性周期蛋白-D1的表达显著增加(P<0.001,P=0.002),而干扰SNRPD1则结果相反(P=0.004,P<0.001)。流式细胞术结果显示SNRPD1加快胃癌细胞G 1/S期转变(P<0.001)。过表达SNRPD1可促进胃癌细胞磷酸化磷脂酰肌醇3-激酶(PI3K)、磷酸化蛋白激酶B(Akt)的表达(P=0.043,P<0.001),而干扰SNRPD1则抑制其表达(P均<0.001)。使用PI3K/Akt信号通路激动剂胰岛素样生长因子1干预后,显著促进了SNRPD1干扰�Objective To investigate the expression of small nuclear ribonucleoprotein D1(SNRPD1)in the gastric cancer tissue and evaluate the predictive value of SNRPD1 expression level for the long-term prognosis of gastric cancer patients and the possible functioning mechanism of SNRPD1.Methods The UALCAN and Gene Expression Profiling Interactive Analysis(GEPIA)were employed to analyze the expression level of SNRPD1 in pan-cancer and its relationship with the prognosis of gastric cancer.The clinical data of 109 patients who underwent radical surgery for gastric cancer from January 2014 to January 2017 in the First Affiliated Hospital of Bengbu Medical University were retrospectively analyzed.Gastric cancer and paracancerous tissue samples were collected,and the expression of SNRPD1 was detected by immunohistochemical staining.Lentiviral transfection was employed to construct the BGC-823 gastric cancer cell models with stable high and low expression of SNRPD1,respectively.The CCK-8 assay and colony formation assay were employed to measure the proliferation of gastric cancer cells,and flow cytometry was used to analyze the cell cycle.Western blotting was employed to determine the expression levels of proteins in the signaling pathway.Results The data from UALCAN and GEPIA showed that SNRPD1 was highly expressed in the tissue of malignant tumors including gastric cancer(P<0.001).The expression level of SNRPD1 in the gastric cancer tissue was higher than that in the paracancerous tissue(P<0.001).Moreover,the expression level of SNRPD1 was positively correlated with the levels of carcinoembryonic antigen(P<0.001),carbohydrate antigen 19-9(P<0.001),G stage(P=0.042),T stage(P=0.002),and N stage(P=0.027)in the patients with gastric cancer.The high expression of SNRPD1 had a predictive value for the long-term prognosis of gastric cancer(P<0.001),and it was an independent risk factor for the death of gastric cancer patients(P=0.003).The results of gene ontology and kyoto encyclopedia of genes and Genomes enrichment analyses showed

关 键 词：胃癌 远期预后 小核核糖核蛋白D1 细胞周期 磷脂酰肌醇3-激酶/蛋白激酶B信号通路 

分 类 号：R735.2[医药卫生—肿瘤]