摘要目的 探讨miR?1231在胰腺癌患者血浆和胰腺癌细胞外泌体中的表达及其临床意义.方法 选取2016年4月至2017年8月在湖南省肿瘤医院确诊为胰腺癌的患者16例,选取16例同期健康志愿者作为正常对照组.收集16例胰腺癌患者和16例健康志愿者的血浆,采用实时荧光定量PCR法检测血浆外泌体中miR?1231的表达,分析外泌体中miR?1231 的表达水平与胰腺癌患者临床病理特征的关系.分析胰腺癌细胞系MIA PaCa?2、PANC?1、SW1990、AsPC?1和BxPc?3以及正常胰腺上皮细胞(人胰腺导管上皮细胞和原代人正常胰腺上皮细胞)外泌体中miR?1231的表达.结果实时荧光定量PCR检测结果显示,胰腺癌患者血浆外泌体中miR?1231的表达水平为1.06±0.46,低于健康志愿者(2.30±0.99),差异有统计学意义(P＜0.05). miR?1231在Ⅰ～Ⅱ期和Ⅲ～Ⅳ期胰腺癌患者血浆外泌体中的表达水平分别为1.515±0.531和0.848±0.224,miR?1231在有、无远处转移的胰腺癌患者血浆外泌体中的表达水平分别为0.757±0.278和1.236±0.461,miR?1231在有、无淋巴结转移的胰腺癌患者血浆外泌体中的表达水平为0.838±0.261和1.337± 0.522,差异均有统计学意义(均P＜0.05).胰腺癌患者血浆外泌体中miR?1231在不同年龄、性别、有无吸烟史、糖链抗原19?9( CA19?9)浓度和肿瘤部位的胰腺癌患者血浆外泌体中的表达水平差异均无统计学意义(均P＞0.05),而在不同淋巴转移情况、不同远处转移情况和不同临床分期的胰腺癌患者血浆外泌体中的表达差异均有统计学意义(均P＜0.05). miR?1231 在胰腺癌细胞外泌体中的表达水平为0.142±0.135,低于正常胰腺上皮细胞(1.127±0.179),差异有统计学意义(P＜0.05).结论 胰腺癌患者血浆和胰腺癌细胞外泌体中miR?1231的低表达可能与胰腺癌的发生发展有关,外泌体中miR?1231的表达可能成为胰腺癌新的诊断标志物或预后因子.

abstractsObjective To investigate the expression and clinical significance of exosomal miR?1231 in plasma of pancreatic cancer (PC) patients and pancreatic cancer cells. Methods A total of 16 patients who were diagnosed with pancreatic cancer in Hunan Cancer Hospital were collected from April 2016 to August 2017. Meanwhile, 16 healthy volunteers were recruited as the healthy control group at the same period. The plasma exosomes were extracted, and the levels of miR?1231 were detected by qRT?PCR in PC and healthy control groups. Moreover, the clinicopathological significance of exosomal miR?1231 expression was analyzed. Furthermore, the expression of exosomal miR?1231 was detected in several pancreatic cancer cells (MIA PaCa?2, PANC?1, SW1990, AsPC?1 and BxPc?3) and two normal pancreatic epithelial cells (HPDE and human primary pancreatic epithelial cell ). Results qRT?PCR results showed that the expression level of miR?1231 in plasma exosomes of pancreatic cancer patients ( 1.06 ± 0.46 ) was significantly lower than that in healthy controls (2.30±0.99; P＜0.05). The levels of exosomal miR?1231 in patients with stage Ⅰ?Ⅱ( 1.515 ± 0.531), no distant metastasis ( 1.236 ± 0.461) and no lymph node metastasis (1.337±0.522) were significantly higher than those with stage Ⅲ?Ⅳ( 0.848± 0.224), distant metastasis (0.757±0.278) and lymph node metastasis (0.838±0.261), respectively (P＜0.05 for all). In addition, there were no correlation between exosomal miR?1231 expression and age, sex, smoking history, CA19?9 levels and tumor sites ( P＞0.05). Furthermore, the expression level of exosomal miR?1231 in pancreatic cancer cell lines (0.142 ± 0.135) was significantly lower than that in normal epithelial cells (1.127±0.179; P＜0.05). Conclusions The downregulation of exosomal miR?1231 in plasma of pancreatic cancer patients and pancreatic cancer cells suggests that it is related to the initiation and development of PC. It may be a new diagnostic and prognostic marker for PC.