【摘要】 背景研究发现微小RNA(miR)在肿瘤调控方面发挥了重要作用,但miR-145在胃癌转移中的作用尚不明确。目的检测miR-145、基质金属蛋白酶9(MMP-9)、基质金属蛋白酶抑制剂1(TIMP-1)在胃癌组织、癌旁组织及转移淋巴结、非转移淋巴结组织中的表达水平,探讨miR-145在胃癌组织中的表达水平及其临床意义。方法选取2014年1月—2015年10月于河北医科大学第四医院外三科住院并行胃癌根治术的患者120例,肿瘤标本切除后取胃癌组织、癌旁组织、淋巴结组织,采用实时荧光定量聚合酶链反应(q PCR)检测胃癌组织、癌旁组织、非转移淋巴结组织、转移淋巴结组织miR-145、MMP-9、TIMP-1 mRNA表达水平。结果胃癌组织、癌旁组织、非转移淋巴结、转移淋巴结组织miR-145、MMP-9、TIMP-1 mRNA表达水平比较,差异均有统计学意义(P<0.001);其中癌旁组织miR-145、TIMP-1 mRNA表达水平高于胃癌组织,MMP-9 mRNA表达水平低于胃癌组织;非转移淋巴结组织miR-145mRNA表达水平低于胃癌组织和癌旁组织,MMP-9 mRNA表达水平低于胃癌组织,TIMP-1 mRNA表达水平高于胃癌组织;转移淋巴结组织miR-145、TIMP-1 mRNA表达水平低于胃癌组织、癌旁组织和非转移淋巴结组织,MMP-9 mRNA表达水平高于胃癌组织、癌旁组织和非转移淋巴结组织(P<0.05)。胃癌组织miR-145 mRNA表达水平与癌旁组织呈正相关(r_s=0.302,P<0.001),转移淋巴结组织miR-145 mRNA表达水平与配对胃癌组织呈正相关(r_s=0.346,P=0.003),非转移淋巴结组织miR-145 mRNA表达水平与配对胃癌组织无线性相关关系(r_s=0.264,P=0.070)。胃癌组织miR-145 mRNA表达水平与MMP-9 mRNA表达水平呈负相关(r_s=-0.403,P<0.001),与TIMP-1 mRNA表达水平呈正相关(r_s=0.294,P=0.001);转移淋巴结组织miR-145 mRNA表达水平与MMP-9 mRNA表达水平呈负相关(r_s=-0.323,P<0.001),与TIMP-1 mRNA表达水平无线性相关关系(r_s=0.165,P=0.072);非转移淋巴结组织miR-145 mRNA表达水平与MMP-9、TIMP-1 mRNA表达水平无线性相关关系(r_s=-0.119,P=0.197;r_s=0.096,P=0.295)。结论 miR-145在胃癌组织及淋巴结组织中表达明显下调,miR-145可能通过调节MMPs家族成员而参与胃癌转移。更多还原

【Abstract】 Background MicroRNAs have been reported as key regulators of various cancers,and miR-145 is one of these microRNAs. However,the mechanism and clinical significance of miR-145 in metastases of gastric cancer remain unknown.Objective To detect the expression of miR-145,matrix metalloproteinase 9( MMP-9),matrix metalloproteinase inhibitor 1( TIMP-1) in gastric cancer tissues,adjacent normal tissues and metastatic lymph node,non- metastatic lymph nodes tissues and explore the expression and clinical significance of miR-145 in gastric cancer tissues. Methods From January 2014 to October 2015,120 patients with gastric cancer were included in the study,who accepted radical gastrectomy in Third Department of Surgery of the Fourth Hospital of Hebei Medical University. The expression of miR-145, MMP-9, TIMP-1 mRNA were examined in gastric cancer tissues,adjacent normal tissues and metastatic lymph node,non- metastatic lymph nodes tissues used quantitative real time polymerase chain reaction( q PCR). Results There were statistically significant difference in the expressions of miR-145,MMP-9,TIMP-1 mRNA in gastric cancer tissues,adjacent normal tissues and metastatic lymph node,non- metastatic lymph nodes tissues( P < 0. 001). The expressions of miR-145,TIMP-1 mRNA in adjacent normal tissues were higher than gastric cancer tissues,and the expression of MMP-9 mRNA in adjacent normal tissues was lower than gastric cancer tissues( P < 0. 05). The expression of miR-145 mRNA in non- metastatic lymph nodes tissues was lower than gastric cancer tissues and adjacent normal tissues. The expressions of MMP-9 mRNA in non- metastatic lymph nodes tissues was lower than gastric cancer tissues. The expression of TIMP-1 mRNA in non- metastatic lymph nodes tissues was higher than gastric cancer tissues. The expression of miR-145,TIMP-1 mRNA in metastatic lymph node tissues were lower than gastric cancer tissues,adjacent normal tissues and non- metastatic lymph nodes tissues. The expressions of MMP-9 mRNA in metastatic lymph nodes was higher than gastric cancer tissues,adjacent normal tissues and non- metastatic lymph nodes tissues( P < 0. 05). A positive relationship was found between the expression of miR-145 mRNA in gastric cancer tissues and adjacent normal tissues( r_s= 0. 302,P < 0. 001). A positive relationship was found between the expressions of miR-145 mRNA in metastatic lymph node tissues and their corresponding gastric cancer tissues( r_s= 0. 346, P = 0. 003). There was no relationship between the expressions of miR-145 mRNA in non- metastatic lymph nodes tissues and their corresponding gastric cancer tissues( r_s= 0. 264,P = 0. 070). A negative relationship was found between the expressions of miR-145 and MMP-9 mRNA in gastric cancer tissues( r_s=- 0. 403,P < 0. 001). A positive relationship was found between the expressions of miR-145 and TIMP-1 mRNA in gastric cancer tissues( r_s= 0. 294,P = 0. 001). A negative relationship was found between the expressions of miR-145 and MMP-9mRNA in metastatic lymph node tissues( r_s=- 0. 323, P < 0. 001). There was no relationship between the expressions of miR-145 and TIMP-1 mRNA in metastatic lymph node tissues( r_s= 0. 165,P = 0. 072). There were no relationship between the expressions of miR-145 and MMP-9,TIMP-1 mRNA in non- metastatic lymph nodes tissues( r_s=- 0. 119,P = 0. 197; r_s= 0. 096,P = 0. 295). Conclusion The expression of miR-145 mRNA was significantly down- regulated in gastric cancer and lymph nodes tissues. The miR-145 might be involved in metastases of gastric cancer by regulating MMPs family.更多还原