Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital, Sydney, Australia.
Sydney Medical School, University of Sydney, Sydney, Australia.
Endocr Pathol. 2019 Jun;30(2):128-133. doi: 10.1007/s12022-019-9570-y.
Pancreatic neuroendocrine tumours (PNETs) are relatively uncommon, accounting for 1-2% of all pancreatic neoplasms. Tumour grade (based on the Ki67 proliferative index and mitotic rate) is associated with metastatic risk across large cohorts; however, predicting the behaviour of individual tumours can be difficult. Therefore, any tool which could further stratify metastatic risk may be clinically beneficial. We sought to investigate microRNA (miRNA) expression as a marker of metastatic disease in PNETs. Tumours from 37 patients, comprising 23 with locoregional disease (L) and 14 with distant metastases (DM), underwent miRNA profiling. In total 506 miRNAs were differentially expressed between the L and DM groups, with four miRNAs (miR-3653 upregulated, and miR-4417, miR-574-3p and miR-664b-3p downregulated) showing statistical significance. A database search demonstrated that miRNA-3653 was associated with ATRX abnormalities. Mean survival between the two groups was correlated with mean expression of miRNA-3653; however, this did not reach statistical significance (p = 0.204). Although this is a small study, we conclude that miRNA-3653 upregulation may be associated with an increased risk of metastatic disease in PNETS, perhaps through interaction with ATRX and the alternate lengthening of telomeres pathway.
胰腺神经内分泌肿瘤（PNETs）相对少见，占所有胰腺肿瘤的 1-2%。肿瘤分级（基于 Ki67 增殖指数和有丝分裂率）与大队列中的转移风险相关；然而，预测单个肿瘤的行为可能很困难。因此，任何能够进一步分层转移风险的工具都可能具有临床益处。我们试图研究 microRNA（miRNA）表达作为 PNETs 转移疾病的标志物。37 例患者的肿瘤（包括 23 例局部区域疾病（L）和 14 例远处转移（DM））进行了 miRNA 谱分析。L 和 DM 组之间有 506 个 miRNA 表达差异，其中四个 miRNA（miR-3653 上调，miR-4417、miR-574-3p 和 miR-664b-3p 下调）具有统计学意义。数据库搜索表明 miRNA-3653 与 ATRX 异常有关。两组之间的平均生存时间与 miRNA-3653 的平均表达相关；然而，这并没有达到统计学意义（p=0.204）。尽管这是一项小型研究，但我们得出结论，miRNA-3653 的上调可能与 PNETS 转移疾病的风险增加有关，可能通过与 ATRX 和端粒的非经典延长途径相互作用。
