目的 探讨TSR2核糖体成熟因子在胃癌中的表达情况及其与胃癌恶性演进的相关性,并分析其潜在的作用机制.方法 纳入105例胃癌患者资料,分析TSR2在胃癌组织中表达水平及其对胃癌恶性进展、术后5年生存率的影响;GO及KEGG富集分析预测TSR2的生物学功能及可能的作用机制;通过慢病毒转染技术上调和下调TSR2在胃癌细胞系(MGC-803)的表达水平,并采用CCK-8、Transwell评估其对MGC-803细胞增殖、侵袭及迁移的影响;Western blot检测p-PI3K、p-AKT表达.结果 TSR2在胃癌组织的表达水平显著低于癌旁组织(P<0.001),且TSR2的表达水平与CEA、CA19-9、T分期及N分期相关(P<0.05).单因素联合多因素分析显示,TSR2低表达(P=0.020)、CEA≥5 μg/L(P=0.021)、CA19-9≥37 kU/L(P=0.001)、T3～T4分期(P=0.039)和N2～N3分期(P=0.027)是独立影响胃癌患者施行根治术后5年生存率的风险因子.生存分析结果显示,TSR2表达水平与胃癌患者术后5年生存率呈正相关(P<0.001).生物信息学富集分析预测TSR2的功能可能与PI3K/AKT信号通路相关.CCK-8和Transwell实验结果显示,上调TSR2可抑制胃癌细胞的增殖、迁移和侵袭(P<0.05),下调则反之(P<0.05).Western blot结果显示过表达TSR2可下调胃癌细胞中磷脂肌醇3激酶(PI3K)和蛋白激酶B(AKT)的磷酸化,敲低则反之(P<0.05).结论 TSR2在胃癌组织中低表达并影响患者预后,其可能与下调PI3K/AKT信号通路抑制胃癌细胞的增殖、侵袭与迁移有关.
Objective To investigate the expression of TSR2 in gastric cancer and explore its correlation with progression of gastric cancer and the possible mechanism.Methods We retrospectively analyzed TSR2 expression in clinical specimens from 105 gastric cancer patients and the impact of TSR2 expression level on disease progression and 5-year postoperative survival of the patients.GO and KEGG enrichment analyses were used to predict the biological functions and mechanisms of TSR2.In gastric cancer MGC-803 cells with lentivirus-mediated TSR2 overexpression or knockdown,the changes in cell proliferation,invasion,and migration were assessed with CCK-8 and Transwell assays,and the expressions of p-PI3K and p-AKT were detected using Western blotting.Results TSR2 expression was significantly lower in gastric cancer tissues than in the adjacent tissues with significant correlations with CEA level,CA19-9 level,and T and N staging(P<0.05).A low TSR2 expression,CEA≥5 μg/L,CA19-9≥37 kU/L,T3-T4 stages,and N2-N3 staged were identified as independent risk factors affecting 5-year survival rate of the patients following radical surgery(P<0.05),and a high TSR2 expression was associated with a higher 5-year survival rate of the patients(P<0.001).Bioinformatics analysis suggested the functional involvement of TSR2 with the PI3K/AKT signaling pathway.MGC-803 cells overexpressing TSR2 showed significantly lowered proliferation,migration,and invasion capacities(P<0.05),while TSR2 knockdown produced the opposite effects(P<0.05).Western blotting showed that TSR2 overexpression reduced the phosphorylation of PI3K and AKT,and TSR2 knockdown caused the opposite changes in MGC-803 cells(P<0.05).Conclusion TSR2 is lowly expressed in gastric cancer tissues to adversely affect the patients'prognosis,and its overexpression inhibits gastric cancer cell proliferation,invasion,and migration possibly by downregulating the PI3K/AKT pathway.
夏勇生;王炼;陈孝华;张雨路;孙奥飞;陈德利
蚌埠医科大学 第一附属医院胃肠外科,安徽 蚌埠 233004||蚌埠医科大学 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 233004蚌埠医科大学临床医学院,安徽 蚌埠 233030蚌埠医科大学 第一附属医院胃肠外科,安徽 蚌埠 233004
胃癌;TSR2核糖体成熟因子;PI3K/AKT;增殖;侵袭
gastric cancer;TSR2 ribosome maturation factor;PI3K/AKT;proliferation;invasion
《南方医科大学学报》 2024 (005)
913-919 / 7
安徽省高校自然科学基金重点项目(KJ2021A0685);蚌埠医科大学2023年度研究生科研创新计划(Byycxz23045)
10.12122/j.issn.1673-4254.2024.05.13
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