| 杨晓敏.miR-29a-3p、基质金属蛋白酶9与幽门螺杆菌感染性胃癌的相关性研究[J].浙江中西医结合杂志,2025,35(2): |
| miR-29a-3p、基质金属蛋白酶9与幽门螺杆菌感染性胃癌的相关性研究 |
| Relationship between miR-29a-3p，MMP-9 and Helicobacter pylori-associated gastric cancer |
| 投稿时间：2023-12-13 修订日期：2024-07-05 |
| DOI： |
| 中文关键词: 【关键词】 miR-29a-3p 基质金属蛋白酶9 幽门螺杆菌 胃癌 |
| 英文关键词: |
| 基金项目:温州市科研项目，编号：Y20210875 |
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| 中文摘要: |
| 【】 目的 探讨miR-29a-3p 、基质金属蛋白酶9(MMP-9)与幽门螺杆菌(Hp)感染性胃癌的关系。方法 选取2012年12月至2015年12月收治的胃癌患者100例,收集肿瘤组织及癌旁正常胃黏膜组织标本,根据肿瘤组织Hp感染情况分为阴性组与阳性组。选取人胃癌细胞MGC-803为对照组,加入Hp菌株共培养,对细胞转染不同物质,分为miR-29a-3p组(转染miR-29a-3p mimic)、miR-29a-3p inhibitor组(转染miR-29a-3p inhibitor)、miR-NC组(转染miR-NC)。对Hp阴性、阳性胃癌组织进行转录组测序,实时荧光定量法检测组织、细胞miR-29a-3p、MMP-9 mRNA表达水平,蛋白质印迹法检测组织、细胞MMP-9蛋白表达水平,分析miR-29a-3p、MMP-9表达水平与临床病理特征、预后的关系,采用多因素Cox回归分析Hp阳性胃癌患者预后不良的影响因素,生物信息学、荧光素酶实验验证miR-29a-3p、MMP-9的靶向关系。结果 Hp阳性、阴性胃癌组织miR-29a-3p表达水平高于正常胃黏膜组织(P<0.05),Hp阳性胃癌组织miR-29a-3p表达水平高于Hp阴性胃癌组织(P<0.05)。Hp阳性胃癌组织MMP-9表达水平低于正常胃黏膜组织(P<0.05),Hp阳性胃癌组织MMP-9表达水平低于Hp阴性胃癌组织(P<0.05)。Hp阳性胃癌组织miR-29a-3p、MMP-9表达水平呈负相关(r=-0.293,P=0.030)。miR-29a-3p、MMP-9表达水平与Hp阳性胃癌患者肿瘤直径、TNM分期、淋巴结转移及远处转移有关(P<0.01)。miR-29a-3p低表达组患者术后5年生存率(51.04%)高于miR-29a-3p高表达组患者(21.45%),差异有统计学意义(P=0.041)。MMP-9高表达组患者术后5年中位生存率(55.32%)高于MMP-9低表达组患者(20.18%),差异有统计学意义(P=0.003)。TNM分期、淋巴结转移、远处转移、miR-29a-3p高表达及MMP-9低表达是Hp阳性胃癌患者预后不良的独立危险因素。miR-29a-3p与MMP-9具有良好的靶向关系。结论 Hp感染性胃癌患者胃癌组织中miR-29a-3p高表达,MMP-9低表达,二者呈负性调控关系,与患者临床病理特征、预后有关,可作为Hp感染性胃癌早期诊断的候选标志物。 |
| 英文摘要: |
| 【】 Objective To investigate the relationship between miR-29a-3p, matrix metalloproteinase-9 (MMP-9) and Helicobacter pylori (HP)-associated gastric cancer. Method 100 patients with gastric cancer from December 2012 to December 2015 were selected. Tumor tissue samples and normal gastric mucosa adjacent to the cancer were collected. Theywere divided into negative group and positive group according to whether HP infection. Human gastric cancer cell line MGC-803 was selected as the control group and infected with HP. According to different transfection substances, it was divided into miR-29a-3p group (transfected miR-29a-3p mimic), miR-29a-3p inhibitor group (transfected miR-29a-3p inhibitor) and miR-NC group (transfected miR-NC). Transcriptome sequencing was performed on HP negative and positive gastric cancer tissues. The expression levels of miR-29a-3p and MMP-9 mRNA in tissues and cells were detected by real-time fluorescence quantitative method. The proteinexpression levels of MMP-9 in tissues and cells were detected by Western blot. The relationships between the expression levels of miR-29a-3p and MMP-9, clinicopathological features and prognosis were analyzed. Multivariate Cox regression was used to analyze the influencing factors of poor prognosis in patients with HP positive gastric cancer. Bioinformatics and luciferase experiments were used to verifythetargeting relationship of miR-29a-3p and MMP-9. Result The expression levels of miR-29a-3p in HP positive and negative gastric cancer tissues were higher than that in normal gastric mucosa tissues (P < 0.05). The expression level of miR-29a-3p in HP positive gastric cancer tissues was higher than that in HP negative gastric cancer tissues (P < 0.05). The expression level of MMP-9 in HP positive gastric cancer tissues was lower than that in normal gastric mucosa tissues (P < 0.05), while the expression level of MMP-9 in HP positive gastric cancer tissues was lower than that in HP negative gastric cancer tissues (P < 0.05). The expression levels of miR-29a-3p in HP positive gastric cancer were negatively correlated with MMP-9 (r=-0.293, P=0.030). The expression levels of miR-29a-3p and MMP-9 were related to tumor diameter, TNM stage, lymph node metastasis and distant metastasis in patients with HP positive gastric cancer (P < 0.01). The median 5-year survival rate (51.04%) of patients with low expression of miR-29a-3p was higher than that of patients with high expression of miR-29a-3p (21.45%) (P=0.041). The median 5-year survival rate of patients with high MMP-9 expression group (55.32%) was higher than that of patients with low MMP-9 expression group (20.18%) (P=0.003). TNM stage, lymph node metastasis, distant metastasis, high expression of miR-29a-3p and low expression of MMP-9 are independent risk factors for poor prognosis in patients with HP positive gastric cancer. miR-29a-3p has a good targeting relationship with MMP-9. Conclusion The high expression of miR-29a-3p and low expression of MMP-9 in gastric cancer tissues of patients with HP-associated gastric cancer have a negative regulatory relationship, which is related to the clinicopathological features and prognosis of patients. They can be used as candidate markers for the early diagnosis of HP-associated gastric cancer. |
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