胰腺癌组织c-MET表达与循环miR-34a、miR-449水平的相关性

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目的:探讨胰腺癌组织织间质表皮转化因子(c-MET)的表达与循环miR-34a、miR-449水平的相关性及其临床意义。方法:收集2015年3月至2017年3月间嘉兴医学院附属第二医院行手术治疗并经病理证实的41例胰腺癌患者的临床资料。通过免疫组织化学染色检测胰腺癌组织及其匹配的癌旁正常胰腺组c-MET表达,根据测定结果将患者分为c-MET阳性组与c-MET阴性组。采集患者手术前和手术后3个月外周血,应用荧光定量PCR法检测循环miR-34a和miR-449水平。分析癌组织c-MET表达与患者临床病理参数、预后及循环miR-34a、miR-449水平的关系。分析循环miR-34a和miR-449水平对胰腺癌TNM分期、淋巴结转移和预后的评估价值。结果:胰腺癌组织c-MET阳性率明显高于癌旁正常组织(63.4%比24.4%),差异有统计学意义(n P<0.05)。与c-MET阴性患者比较,c-MET阳性患者TNMⅢ/Ⅳ期者居多(73.1%比33.4%),淋巴结转移率高(76.9%比46.7%),生存时间短(29.5个月比35.0个月),生存率低(38.5%比53.3%),差异均有统计学意义(n P值均<0.05)。术前c-MET阳性患者循环miR-34a、miR-449水平明显低于c-MET阴性患者(0.228±0.068比0.524±0.106、0.252±0.063比0.432±0.094,n P<0.05),术后c-MET阳性患者循环miR-449水平仍明显低于c-MET阴性患者(0.414±0.088比0.512±0.114,n P<0.05),但两组间miR-34a水平的差异无统计学意义。术前循环miR-34a、miR-449水平对胰腺癌TNM分期、淋巴结转移及预后有预测价值(n P<0.05)。n 结论:miR-34a、miR-449靶向结合胰腺癌组织c-MET,有可能成为潜在的胰腺癌标志物。“,”Objective:To investigate the correlation of c-MET expression with circulating miR-34a and miR-449 level in pancreatic cancer tissue and its clinical significance.Methods:A total of 41 patients with pancreatic cancer treated surgically and pathologically confirmed from March 2015 to March 2017 were collected in Second Affiliated Hospital of Jiaxing Medical College. The expression of hepatocyte growth factor receptor (c-MET) in pathological tissues and matching adjacent normal tissues was determined by immunohistochemistry. The patients were divided into c-MET positive group (n n=26) and c-MET negative group (n n=15) according to the results. Peripheral blood was collected before and 3 months after the operation, and the expressions of circulating miRNA34a (miR-34a) and miR-449 were determined by fluorescence quantitative PCR. The relationships between c-MET in pancreatic cancer tissue and clinicopathological features, prognosis, circulating miR-34a expression, and miR-449 expression were analyzed. The effects of circulating miR-34a and miR-449 expression on TNM stage, lymph node metastasis and prognosis of pancreatic cancer patients were analyzed.n Results:The positive rate of c-MET in pancreatic cancer was obviously higher than that in adjacent normal tissue (63.4% n vs 24.4%), and the difference was statistically significant (n P<0.05). Compared with c-MET negative group, the TNM stage Ⅲ/Ⅳ cases in c-MET positive group were more (73.1%n vs 33.4%), the lymph node metastasis rate in c-MET positive group (76.9% n vs 46.7%) were higher, and the follow-up survival time of c-MET positive group was shorter (29.5 mo n vs 35 mo), and the survival rate of the c-MET positive group was lower (38.5% n vs 53.3%), and the differences were statistically significant (all n P<0.05). Before surgery, the expressions of circulating miR-34a and miR-449 in the c-MET positive group were lower than those in the c-MET negative group (0.228±0.068n vs 0.524±0.106, 0.252± 0.063 n vs 0.432±0.094, n P<0.05). After surgery, the miR-449 expression in c-MET positive group was still lower than that in c-MET negative group (0.414±0.088n vs 0.512±0.114, n P<0.05), while there was no statistically significant difference on miR-34a between the two groups. Preoperative miR-34a and miR-449 expression had predictive value for TNM stage, lymphatic metastasis and prognosis (n P<0.05).n Conclusions:miR-34a and miR-449 may target c-MET in pancreatic cancer tissue, which could be used as potential tumor markers for pancreatic cancer.
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