| 引用本文: | 黄珊珮,韦二丹,朱丽叶,宁绮婷,陈形梅,陈妮,吴江妮,丘新泽,黄杰安,刘诗权.FTO、GSDMD与胃癌转移的关联性分析及作用机制研究[J].中国临床新医学,0,():-. |
| Huang Shan-pei,Wei Er-dan,Zhu Li-ye,Ning Qi-ting,Chen Xing-mei,Chen Ni,Wu Jiang-ni,Qiu Xin-ze,Huang Jie-an.FTO、GSDMD与胃癌转移的关联性分析及作用机制研究[J].中国临床新医学,0,():-. |
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| FTO、GSDMD与胃癌转移的关联性分析及作用机制研究 |
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黄珊珮, 韦二丹, 朱丽叶, 宁绮婷, 陈形梅, 陈妮, 吴江妮, 丘新泽, 黄杰安, 刘诗权
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广西医科大学第二附属医院
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| 摘要: |
| 目的 探讨胃癌组织中肥胖相关蛋白（fat mass and obesity-associated protein，FTO）与消皮素D（gasdermin D, GSDMD）表达的相关性，以及FTO调控GSDMD对胃癌细胞迁移的影响。方法 利用TIMER 2.0在线数据库分析FTO与GSDMD在泛癌中的表达情况。收集2022年1月至2023年3月在广西医科大学第二附属医院接受手术治疗的45例胃癌患者的胃癌组织样本及对应癌旁组织样本，并收集对应患者的临床资料。采用免疫组织化学染色法检测组织中FTO及GSDMD的表达情况，分析两者的相关性及其与患者临床病理特征的关联性。构建胃癌AGS细胞稳定低表达 FTO细胞株，采用实时荧光定量聚合酶链式反应（RT-qPCR）法检测FTO低表达细胞株中GSDMD mRNA的表达情况；采用细胞划痕及细胞迁移实验检测低表达FTO对胃癌细胞迁移的影响。结果 TIMER 2.0数据库与免疫组织化学的分析结果显示FTO及GSDMD均在胃癌组织中高表达，差异具有统计学意义（P<0.05）；FTO和GSDMD高表达组均与肿瘤的侵犯深度、淋巴结转移密切相关（P<0.05）。Kappa一致性检验结果表明胃癌中FTO与GSDMD的表达有一致性（P=0.012）。RT-qPCR检测显示抑制FTO表达显著抑制GSDMD mRNA的表达（t=40.68，P<0.0001）。相比于对照组细胞，低表达FTO组胃癌细胞划痕愈合率及迁移数明显减少，差异具有统计学意义（t=10.25，P=0.0005；t=4.571，P=0.0103）。结论 FTO可能通过调控GSDMD的表达促进胃癌细胞的转移。 |
| 关键词: 胃癌、肥胖相关蛋白、消皮素D、细胞迁移 |
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| 基金项目:国家自然科学基金项目（编号：82260579）；国家自然科学基金项目（编号：81460380）；广西医学高层次骨干人才培养“139”计划培养人选项目(编号:G202003016)；广西中医药适宜技术开发与推广项目(编号:GZSY21-56)；广西研究生教育创新计划项目(编号：YCSW2023240) |
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| Analysis of the association between FTO, GSDMD and gastric cancer metastasis and its mechanism of action |
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Huang Shan-pei, Wei Er-dan, Zhu Li-ye, Ning Qi-ting, Chen Xing-mei, Chen Ni, Wu Jiang-ni, Qiu Xin-ze, Huang Jie-an
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the Second Affiliated Hospital of Guangxi Medical University
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| Abstract: |
| Objective To investigate the correlation between fat mass and obesity-associated protein (FTO) and gasdermin D (GSDMD) expression in gastric cancer tissues, and the effect of FTO regulation of GSDMD on gastric cancer cell migration. Methods The TIMER 2.0 online database was used to analyze the expression of FTO and GSDMD in pan-carcinoma. Collected tissue samples from 45 cases of gastric cancer patients and corresponding paracancerous tissue samples who underwent surgery in the Second Affiliated Hospital of Guangxi Medical University from January 2022 to March 2023, and collected clinical data of corresponding patients. The expression of FTO and GSDMD in tissues was detected by immunohistochemical staining, and the correlation between the two and its association with the clinicopathological features of patients was analyzed. A stable low-expression FTO cell line for gastric cancer AGS cells was constructed, and the expression of GSDMD mRNA in FTO low-expression cell line was detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell scratch and cell migration experiments were used to investigate the effect of low expression FTO on gastric cancer cell migration. Results The results of TIMER 2.0 database and immunohistochemistry showed that FTO and GSDMD were highly expressed in gastric cancer tissues, and the difference was statistically significant (P<0.05); Both FTO and GSDMD high expression groups were closely associated with tumor invasion depth and lymph node metastasis (P<0.05). The results of Kappa consistency analysis showed that the expressions of FTO and GSDMD were consistent in gastric cancer (P=0.012). RT-qPCR showed that the expression of GSDMD mRNA was significantly inhibited by inhibition of FTO expression (t=40.68, P<0.0001). Compared with the control group, the scratch healing rate and migration number of gastric cancer cells in the low-expression FTO group were significantly reduced, and the difference was statistically significant (t=10.25, P=0.0005; t=4.571, P=0.0103). Conclusion FTO may promote the metastasis of gastric cancer cells by regulating the expression of GSDMD. |
| Key words: Gastric cancer Fat mass and obesity-associated protein Gasdermin D Cell migration |
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