AKR7A3在胃癌中的表达、细胞生物学影响及临床意义研究OACSTPCD
AKR7A3 expression in gastric cancer,its biological function and clinical significance
背景 AKR7A3 是一种新发现的肿瘤相关分子,在癌症的发生、发展中起着非常重要的作用,但其在胃癌(gastric carcinoma,GC)中的作用研究较少.目的 探讨AKR7A3对于胃癌的临床意义及预后预测价值,并通过体外细胞学实验分析验证其对胃癌细胞生物学功能的影响.方法 利用TCGA、GEPIA、GDSC等数据库及R语言软件,采用生物信息学方法分析AKR7A3对胃癌患者临床预后及用药等方面的影响,并采用什么细胞系,通过体外细胞实验CCK-8检测细胞增殖,划痕实验检测细胞迁移,流式细胞实验检测细胞凋亡.验证AKR7A3对胃癌细胞的生物学功能的影响.结果 差异性分析可见AKR7A3在胃癌组织中表达下调(P<0.05),并且预后分析提示低表达组胃癌患者总生存期及无病生存期均低于高表达组(P<0.05),对胃癌患者预后的预测具有指导意义,AKR7A3可能通过Nitrogen metabolism等信号通路影响胃癌的发生发展,并与Salubrinal、拉帕提尼等化疗药物敏感性相关,并且AKR7A3能够抑制细胞增殖(P<0.05)、促进细胞凋亡(P<0.05),同时还能抑制细胞迁移(P<0.01),使MDA含量增加(P<0.05).结论 AKR7A3可能与胃癌患者预后、化疗药物选择及疗效等有关,并且在胃癌细胞中作为抑癌基因,能够抑制肿瘤细胞的增殖、迁移,促进细胞凋亡.
Background AKR7A3 is a newly identified tumor-associated molecule that plays a very important role in the occurrence and development of cancer.However,its role in gastric carcinoma(GC)has been less studied.Objective To investigate the clinical significance and prognostic value of AKR7A3 in gastric cancer and verify its impact on the biological functions of gastric cancer cells through in vitro cytological experiments.Methods In our study,different databases and tools,including GEPIA,TCGA,GDSC and R software,were applied to analyze the impact of AKR7A3 on clinical prognosis and medication effects.The CCK8 assay was used to detect cell proliferation,the scratch assay to measure cell migration,the Transwell assay to assess cell migration and invasion,and flow cytometry to evaluate apoptosis and cell cycle.The biological functions of AKR7A3 in gastric cancer cells were validated through in vitro cellular experiments.Results The expression of AKR7A3 was down-regulated in GC tissues significantly(P<0.05).Furthermore,patients in low AKR7A3 expression group had shorter overall survival and worse disease-free survival(DFS)than those in high expression group(P<0.05).Based on the findings,AKR7A3 might have predictive value of clinical prognosis,and might affect the occurrence and development of gastric cancer through signaling pathways such as Nitrogen metabolism,which was associated with the sensitivity of chemotherapy drugs such as salubrinal and lapatinib.In addition,AKR7A3 was able to inhibit cell proliferation,promote apoptosis,suppress cell migration and increase MDA levels.Conclusion AKR7A3 plays an important role in the prognosis,chemotherapeutic selection and the therapeutic efficacy in gastric cancer patients.As a tumour suppressor gene in gastric cancer cells,it can inhibit tumour cell proliferation and migration and promote apoptosis.
杨斯茗;许尹梅;李建雄
解放军总医院研究生院,北京 100853解放军总医院第五医学中心肿瘤学部,北京 100039
临床医学
AKR7A3胃癌预后生物学功能蛋白质组学
AKR7A3gastric carcinomaprognosisbiological functionproteomics
《解放军医学院学报》 2024 (008)
868-877,885 / 11
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