Hao Sijie, Yao Lie, Huang Jiaxin, He Hang, Yang Feng, Di Yang, Jin Chen, Fu Deliang
1 Department of Pancreatic Surgery, Huashan Hospital, Fudan University, Shanghai, China.
Technol Cancer Res Treat. 2018 Jan 1;17:1533034617748429. doi: 10.1177/1533034617748429.
Long noncoding RNAs have been shown to play crucial roles in cancer biology, while the long noncoding RNA landscapes of pancreatic ductal adenocarcinoma have not been completely characterized. We aimed to determine whether long noncoding RNA could serve as early diagnostic biomarkers for pancreatic ductal adenocarcinoma.
We conducted a genome-wide microarray analysis on pancreatic ductal adenocarcinoma and their adjacent noncancerous tissues from 8 Chinese patients.
A total of 3352 significantly differentially expressed long noncoding RNAs were detected. Of total, 1249 long noncoding RNAs were upregulated and 2103 were downregulated (fold change ≥2, P < 0.05, FDR <0.05). These differentially expressed long noncoding RNAs were not evenly distributed among chromosomes in human genome. Hierarchical clustering of these differentially expressed long noncoding RNAs revealed large variabilities in long noncoding RNA expression among individual patient, indicating that certain long noncoding RNAs could play a unique role or be used as a biomarker for specific subtype of pancreatic ductal adenocarcinoma. Gene Ontology enrichment and pathway analysis identified several remarkably dysregulated pathways in pancreatic ductal adenocarcinoma tissue, such as interferon-γ-mediated signaling pathway, mitotic cell cycle and proliferation, extracellular matrix receptor interaction, focal adhesion, and regulation of actin cytoskeleton. The co-expression network analysis detected 393 potential interactions between 80 differentially expressed long noncoding RNAs and 105 messenger RNAs. We experimentally verified 7 most markedly dysregulated long noncoding RNAs from the network.
Our study provided a genome-wide survey of dysregulated long noncoding RNAs and long noncoding RNA/messenger RNA co-regulation networks in pancreatic ductal adenocarcinoma tissue. These dysregulated long noncoding RNA/messenger RNA networks could be used as biomarkers to provide early diagnosis of pancreatic ductal adenocarcinoma or its subtype, predict prognosis, and evaluate treatment efficacy.
长链非编码RNA已被证明在癌症生物学中发挥关键作用，而胰腺导管腺癌的长链非编码RNA图谱尚未完全明确。我们旨在确定长链非编码RNA是否可作为胰腺导管腺癌的早期诊断生物标志物。
我们对8例中国患者的胰腺导管腺癌及其癌旁非癌组织进行了全基因组微阵列分析。
共检测到3352个显著差异表达的长链非编码RNA。其中，1249个长链非编码RNA上调，2103个下调（倍数变化≥2，P<0.05，FDR<0.05）。这些差异表达的长链非编码RNA在人类基因组的染色体中分布不均。对这些差异表达的长链非编码RNA进行层次聚类分析，结果显示个体患者之间长链非编码RNA表达存在较大差异，这表明某些长链非编码RNA可能发挥独特作用或可作为胰腺导管腺癌特定亚型的生物标志物。基因本体富集分析和通路分析确定了胰腺导管腺癌组织中一些明显失调的通路，如干扰素-γ介导的信号通路、有丝分裂细胞周期和增殖、细胞外基质受体相互作用、粘着斑以及肌动蛋白细胞骨架的调节。共表达网络分析检测到80个差异表达的长链非编码RNA与105个信使RNA之间存在393个潜在相互作用。我们通过实验验证了该网络中7个失调最为明显的长链非编码RNA。
我们的研究对胰腺导管腺癌组织中失调的长链非编码RNA以及长链非编码RNA/信使RNA共调控网络进行了全基因组调查。这些失调的长链非编码RNA/信使RNA网络可作为生物标志物，用于胰腺导管腺癌或其亚型的早期诊断、预测预后以及评估治疗效果。
