Ge Xianxiu, Wang Youli, Nie Junjie, Li Quanpeng, Tang Lingyu, Deng Xueting, Wang Fei, Xu Boming, Wu Xiaochao, Zhang Xiuhua, You Qiang, Miao Lin
Institute of Digestive Endoscopy and Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Clinical Laboratory, Nanjing First Hospital, Nanjing, China.
Oncotarget. 2017 Jul 25;8(41):69995-70005. doi: 10.18632/oncotarget.19547. eCollection 2017 Sep 19.
Cholangiocarcinoma (CCA) is an aggressive malignancy associated with unfavorable prognosis, and it's difficult to diagnose and no effective treatments are available. Long non-coding RNAs (lncRNAs) play important roles in tumorigenesis and metastasis. Intact lncRNAs from exosomes have sparked much interest as potential biomarker for the non-invasive analysis of disease. Here, via exosome sequencing on lncRNAs, GO analysis, KEGG pathway and co-expression analysis, receiver operating characteristic curve and survival analyses, we found that, compared with control group, lncRNAs of ENST00000588480.1 and ENST00000517758.1 showed significantly increased expressions in CCA group. Moreover, area under the curve (AUC) was increased to 0.709 when combined the two lncRNAs, they had a sensitivity and specificity of 82.9% and 58.9% respectively. Further, the higher levels of the two lncRNAs showed a significantly increasing trend with the advancement of cancer TNM stages, and prognosticated a poor survival. In addition, KEGG pathway analysis showed that the most significant difference term was "p53 signaling pathway" (KEGG ID: hsa04115, p: 0.001). The altered lncRNAs and their target genes were included to reconstruct a co-expression network. These altered lncRNAs were mainly related to cellular processes, environmental information processing and organismal systems, etc. Collectively, our findings provided the potential roles of lncRNAs of ENST00000588480.1 and ENST00000517758.1 in CCA, and implicated these lncRNAs as potential diagnostic and therapeutic targets for CCA.
胆管癌（CCA）是一种侵袭性恶性肿瘤，预后不良，难以诊断且尚无有效的治疗方法。长链非编码RNA（lncRNA）在肿瘤发生和转移中起重要作用。外泌体中的完整lncRNA作为疾病非侵入性分析的潜在生物标志物引发了广泛关注。在此，通过对lncRNA进行外泌体测序、基因本体（GO）分析、京都基因与基因组百科全书（KEGG）通路及共表达分析、受试者工作特征曲线和生存分析，我们发现，与对照组相比，ENST00000588480.1和ENST00000517758.1的lncRNA在CCA组中表达显著增加。此外，将这两种lncRNA联合使用时，曲线下面积（AUC）增至0.709，其灵敏度和特异性分别为82.9%和58.9%。进一步研究发现，这两种lncRNA的较高水平随癌症TNM分期的进展呈显著上升趋势，且预示着较差的生存率。此外，KEGG通路分析显示，最显著差异的条目是“p53信号通路”（KEGG ID：hsa04115，p：0.001）。纳入改变的lncRNA及其靶基因以重建共表达网络。这些改变的lncRNA主要与细胞过程、环境信息处理和生物系统等相关。总的来说，我们的研究结果揭示了ENST00000588480.1和ENST00000517758.1的lncRNA在CCA中的潜在作用，并表明这些lncRNA作为CCA潜在的诊断和治疗靶点。
