Wang Yingyi, Yang Yuemei, Wang Yanfeng, Li Xiaoou, Xiao Yu, Wang Wenze
Department of Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Front Cell Dev Biol. 2020 Jun 4;8:392. doi: 10.3389/fcell.2020.00392. eCollection 2020.
The aim of this study was to explore the association between the expression of a long non-coding RNA (lncRNA), cancer susceptibility candidate 8 (CASC8), and pancreatic adenocarcinoma (PAAD).
starBase database was used to perform differential expression, survival, and competing endogenous RNA (ceRNA) network and H19/miR-671 correlation analyses for CASC8 in 178 PAAD samples. Using the cBioPortal database website, we analyzed the alteration in CASC8 expression and its correlation with the overall survival in PAAD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were also performed using the circlncRNAnet database. Analysis of CASC8 polymorphisms was performed using the UCSC Xena database. Finally, the expression of CASC8 in Chinese PAAD tissues was validated by qPCR.
The expression of CASC8 was observed to be high in 178 PAAD samples [fold change = 8.71, = 0.0014, false discovery rate (FDR) = 0.04] and was related with poor prognosis, but not in pancreatic neuroendocrine tumor (pNET). CASC8 amplification was noted in 6% of the PAAD patients; however, the gene amplification did not affect the expression of CASC8 but was involved with the overall survival time of PAAD patients. Network analysis indicated that H19 is the ceRNA pair of CASC8 and that CASC8 competitively binds to miR-671 and might participate in the process of epithelial-to-mesenchymal transition (EMT). The correlation analysis showed that CASC8 was significantly negatively correlated with SMAD7. The analysis of CASC8 polymorphism showed that high copy number segment (CNS) of CASC8 is associated with low survival. Validation using PAAD tissues from Chinese patients was consistent with the findings.
CASC8 is specifically expressed at a high level in PAAD and associated with poor prognosis, which might be through its interaction with H19, miR-671, and SMAD7. These results indicate that CASC8 could serve as a novel marker for predicting the prognosis and as a potential target for the therapy of PAAD.
本研究旨在探讨长链非编码RNA（lncRNA）癌症易感性候选基因8（CASC8）的表达与胰腺腺癌（PAAD）之间的关联。
利用starBase数据库对178例PAAD样本中的CASC8进行差异表达、生存及竞争性内源RNA（ceRNA）网络和H19/miR-671相关性分析。通过cBioPortal数据库网站，分析PAAD中CASC8表达的改变及其与总生存期的相关性。还使用circlncRNAnet数据库进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析。利用UCSC Xena数据库对CASC8多态性进行分析。最后，通过qPCR验证CASC8在中国PAAD组织中的表达。
在178例PAAD样本中观察到CASC8表达较高[倍数变化=8.71， =0.0014，错误发现率（FDR）=0.04]，且与预后不良相关，但在胰腺神经内分泌肿瘤（pNET）中并非如此。在6%的PAAD患者中发现CASC8扩增；然而，基因扩增并不影响CASC8的表达，但与PAAD患者的总生存时间有关。网络分析表明，H19是CASC8的ceRNA对，且CASC8竞争性结合miR-671并可能参与上皮-间质转化（EMT）过程。相关性分析表明，CASC8与SMAD7显著负相关。CASC8多态性分析表明，CASC8的高拷贝数片段（CNS）与低生存率相关。对中国患者的PAAD组织进行验证与上述结果一致。
CASC8在PAAD中特异性高表达并与预后不良相关，这可能是通过其与H19、miR-671和SMAD7的相互作用实现的。这些结果表明，CASC8可作为预测预后的新型标志物及PAAD治疗的潜在靶点。
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