High expression of AFAP1-AS1 is associated with poor survival and short-term recurrence in pancreatic ductal adenocarcinoma.
High expression of AFAP1-AS1 is associated with poor survival and short-term recurrence in pancreatic ductal adenocarcinoma.
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AFAP1-AS1的高表达与胰腺导管腺癌的不良生存和短期复发相关
DOI：
10.1186/s12967-015-0490-4
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发表时间：
2015-04-30
影响因子：
7.4
通讯作者：
Chen R
中科院分区：
文献类型：
--
作者：
Ye Y;Chen J;Zhou Y;Fu Z;Zhou Q;Wang Y;Gao W;Zheng S;Zhao X;Chen T;Chen R
胰腺导管腺癌（PDAC）仍然是一种致命的恶性肿瘤。长链非编码RNA（lncRNA）已被证明在癌症的发展和进展中起关键作用。在此，我们鉴定了lncRNA AFAP 1-AS 1在PDAC患者中的过表达，并评估了其预后和功能相关性。通过lncRNA微阵列测量PDAC中的整体lncRNA表达谱。采用逆转录定量聚合酶链反应（RT-qPCR）检测90例PDAC组织及癌旁正常组织中AFAP 1-AS 1的表达。使用敲低和异位表达策略在体外评估AFAP 1-AS 1表达对细胞增殖、迁移和侵袭的影响。基因芯片分析显示，AFAP 1-AS 1在PDAC组织中的表达高于正常组织，RT-qPCR证实69/90例（76.7%）。其过表达与淋巴结转移、神经浸润和生存率低有关。以AFAP 1-AS 1作为预后指标，预测6个月和1年内肿瘤进展的ROC曲线下面积分别为0.8669和0.9370。在体外功能实验中，涉及敲低AFAP 1-AS 1导致PDAC细胞增殖、迁移和侵袭减弱。AFAP 1-AS 1的异位表达促进细胞增殖、迁移和侵袭。AFAP 1-AS 1是一个潜在的新的预后指标，预测PDAC患者术后的临床结果，并可能是一个合理的治疗目标。本文的在线版本（doi：10.1186/s12967-015-0490-4）包含补充材料，可供授权用户使用。
Pancreatic ductal adenocarcinoma (PDAC) is still a lethal malignancy. Long noncoding RNAs (lncRNAs) have been shown to play a critical role in cancer development and progression. Here we identified overexpression of the lncRNA AFAP1-AS1 in PDAC patients and evaluated its prognostic and functional relevance. The global lncRNA expression profile in PDAC was measured by lncRNA microarray. Expression of AFAP1-AS1 was evaluated by reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) in 90 PDAC tissue samples and adjacent normal tissues. The impact of AFAP1-AS1 expression on cell proliferation, migration, and invasion were evaluated in vitro using knockdown and ectopic expression strategies. Microarray analysis revealed that up-regulation of AFAP1-AS1 expression in PDAC tissues compared with normal adjacent tissues, which was confirmed by RT-qPCR in 69/90 cases (76.7%). Its overexpression was associated with lymph node metastasis, perineural invasion, and poor survival. When using AFAP1-AS1 as a prognostic marker, the areas under ROC curves were 0.8669 and 0.9370 for predicting tumor progression within 6 months and 1 year, respectively. In vitro functional experiments involving knockdown of AFAP1-AS1 resulted in attenuated PDAC cell proliferation, migration, and invasion. Ectopic expression of AFAP1-AS1 promoted cell proliferation, migration, and invasion. AFAP1-AS1 is a potential novel prognostic marker to predict the clinical outcome of PDAC patients after surgery and may be a rational target for therapy. The online version of this article (doi:10.1186/s12967-015-0490-4) contains supplementary material, which is available to authorized users.
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