胰腺癌组织miRNA let-7a与HMGA2的表达及血清miRNA let-7a水平对胰腺癌的诊断价值

毛兴波; 盛涛; 庄丽萍; 邬长康; 赵国刚

doi:10.12182/20200760107

胰腺癌组织miRNA let-7a与HMGA2的表达及血清miRNA let-7a水平对胰腺癌的诊断价值

Expression of miRNA let-7a and HMGA2 and Diagnostic Value of Serum miRNA let-7a Level in Pancreatic Cancer

摘要

摘要:
目的探讨胰腺癌组织中miRNA let-7a、高迁移率族蛋白2（high mobility group A2，HMGA2）的表达情况及血清miRNA let-7a水平在胰腺癌中的诊断价值。
方法回顾性收集我科2014年1月−2019月1月行手术治疗的60例胰腺癌患者术中获得的新鲜胰腺导管腺癌组织及癌旁正常胰腺组织，同时收集胰腺癌患者手术前后血清标本，并收集同期于我院体检的60例体检结果正常者的血清标本作为对照组。采用实时荧光定量PCR法检测健康体检者及患者血清标本miRNA let-7a表达，癌组织、癌旁正常组织miRNA let-7a和HMGA 2 mRNA表达，Western blot法检测患者癌组织、癌旁正常组织HMGA2蛋白的表达。分析血清miRNA let-7a水平，癌组织miRNA let-7a、HMGA2 mRNA 表达与胰腺癌临床病理特征的关联，并用受试者工作特征曲线分析术前血清miRNA let-7a水平对胰腺癌的诊断价值。
结果与癌旁正常组织相比，胰腺癌组织中miRNA let-7a表达水平下降（t=20.291，P<0.01），HMGA2 mRNA表达上升（t=46.681，P<0.01）；癌组织HMGA2蛋白表达较癌旁正常组织增高（t=22.973，P<0.01）。miRNA let-7a在胰腺癌患者血清中的表达较健康对照者降低（t=24.854，P<0.01）；在胰腺癌患者术后1周血清中miRNA let-7a相对表达量较术前下降（t=6.885，P<0.01）；癌组织与术前血清中miRNA let-7a表达量呈正相关（r=0.411，P=0.000）。胰腺癌中miRNA let-7a、HMGA2 mRNA水平在不同TNM分期及有无淋巴结转移间差异均有统计学意义(P<0.05)。以术前血清miRNA let-7a诊断胰腺癌的曲线下面积为0.823，95%置信区间为0.665~0.917，取0.614为最佳临界值，对应的灵敏度为82.3%，特异度为74.1%。
结论胰腺癌组织和血清miRNA let-7a均出现下调，可能通过调控HMGA2的表达参与肿瘤的侵袭和转移；血清miRNA let-7a水平可为胰腺癌的诊断及术后病情监测提供一定的参考。

Abstract:
Objective To investigate the diagnostic value of miRNA let-7a, high mobility group A2 (HMGA2) expression and serum miRNA let-7a level in pancreatic cancer.
Methods From January 2014 to January 2019, 60 patients with pancreatic cancer were collected for fresh pancreatic ductal adenocarcinoma tissue and normal pancreatic tissue adjacent to the cancer after the operation. Serum samples before and after operation were also collected, while 60 healthy people were enrolled as the control group. The expression of miRNA let-7a (qRT-PCR) and HMGA2 (qRT-PCR and Western blot) in cancer and adjacent normal tissues were measured. The serum level of miRNA let-7a was detected by qRT-PCR. The relationship between miRNA let-7a and HMGA2 expression and the clinicopathological features of pancreatic cancer was analyzed. The diagnostic value of serum miRNA let-7a pre-operation in patients with pancreatic cancer was also analyzed with ROC curve.
Results Compared with normal tissues adjacent to the cancer, the expression level of miRNA let-7a in pancreatic cancer tissues decreased (t=20.291, P<0.01), and the expression of HMGA2 mRNA increased (t=46.681, P<0.01). The expression of HMGA2 protein in cancer tissues was higher than that in normal tissues adjacent to the cancer (t=22.973, P<0.01). The serum level of miRNA let-7a in pancreatic cancer patients was significantly lower than that in healthy controls (t=24.854, P<0.01). The relative level of serum miRNA let-7a at 1 week after surgery was significantly lower than that before surgery in pancreatic cancer patients (t=6.885, P<0.01). There was a positive correlation between cancer tissue and serum miRNA let-7a expression 1 week after surgery (r=0.411, P=0.000). The relative expression levels of miRNA let-7a and HMGA2 in pancreatic cancer tissues were significantly different in different TNM stages and lymph node metastasis (P<0.05). The area under curve of pre-operation serum miRNA let-7a for the diagnosis of pancreatic cancer was 0.823 ( 95% confidence interval: 0.665-0.917); when the optimal cut-off value of miRNA let-7a was 0.614, the sensitivity was 82.3%, the specificity was 74.1%.
Conclusion The expression of HMGA2 may be involved in the invasion and metastasis of pancreatic cancer. The level of serum miRNA let-7a may provide a reference for the diagnosis and postoperative monitoring of pancreatic cancer.

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