Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Road, Shanghai 200127, P.R. China.
State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology &Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai cancer Institute, Shanghai Institute of Digestive Diseases, 145 Middle Shandong Road, Shanghai 200001, P.R. China.
Sci Rep. 2016 Sep 15;6:33535. doi: 10.1038/srep33535.
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive and lethal malignancies. Long non-coding RNAs (lncRNAs) are a novel class of non-protein-coding transcripts that have been implicated in cancer biogenesis and prognosis. By repurposing microarray probes, we herein analysed the lncRNA expression profiles in two public PDAC microarray datasets and identified 34 dysregulated lncRNAs in PDAC. In addition, the expression of 6 selected lncRNAs was confirmed in Ren Ji cohort and pancreatic cell lines, and their association with 80 PDAC patients' clinicopathological features and prognosis was investigated. Results indicated that AFAP1-AS1, UCA1 and ENSG00000218510 might be involved in PDAC progression and significantly associated with overall survival of PDAC. UCA1 and ENSG00000218510 expression status may serve as independent prognostic biomarkers for overall survival of PDAC. Gene set enrichment analysis (GSEA) analysis suggested that high AFAP1-AS1, UCA1 and low ENSG00000218510 expression were correlated with several tumorigenesis related pathways. Functional experiments demonstrated that AFAP1-AS1 and UCA1 were required for efficient invasion and/or proliferation promotion in PDAC cell lines, while ENSG00000218510 acted the opposite. Our findings provide novel information on lncRNAs expression profiles which might be beneficial to the precise diagnosis, subcategorization and ultimately, the individualized therapy of PDAC.
胰腺导管腺癌（PDAC）仍然是最具侵袭性和致命性的恶性肿瘤之一。长非编码 RNA（lncRNA）是一类新型的非蛋白编码转录本，它们与癌症的发生和预后有关。通过重新利用微阵列探针，我们在此分析了两个公共 PDAC 微阵列数据集的 lncRNA 表达谱，并在 PDAC 中鉴定出 34 个失调的 lncRNA。此外，在仁济队列和胰腺细胞系中验证了 6 个选定的 lncRNA 的表达，并研究了它们与 80 名 PDAC 患者临床病理特征和预后的关系。结果表明，AFAP1-AS1、UCA1 和 ENSG00000218510 可能参与 PDAC 进展，并与 PDAC 的总生存率显著相关。UCA1 和 ENSG00000218510 的表达状态可能是 PDAC 总生存率的独立预后生物标志物。基因集富集分析（GSEA）分析表明，AFAP1-AS1、UCA1 高表达和 ENSG00000218510 低表达与几种肿瘤发生相关途径相关。功能实验表明，AFAP1-AS1 和 UCA1 是 PDAC 细胞系中有效侵袭和/或增殖促进所必需的，而 ENSG00000218510 则起到相反的作用。我们的研究结果提供了 lncRNA 表达谱的新信息，这可能有助于 PDAC 的精确诊断、分类，最终实现个体化治疗。
