High Cancer Susceptibility Candidate 8 Expression Is Associated With Poor Prognosis of Pancreatic Adenocarcinoma: Validated Analysis Based on Four Cancer Databases

Frontiers in Cell and Developmental Biology

Yingyi Wang¹  Xiaoou Li²  Yanfeng Wang³  Wenze Wang⁴  Yu Xiao⁴  Yuemei Yang⁵ 

[1] Department of Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China;Department of Pathology, Daxing Hospital Affiliated to Capital Medical University, Beijing, China;Department of Pathology, Heilongjiang Province Land Reclamation Headquarter General Hospital, Harbin, China;Department of Pathology, 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;

关键词: long non-coding RNA;    cancer susceptibility candidate 8;    pancreatic adenocarcinoma;    competing endogenous RNA;    miRNA;   

DOI  :  10.3389/fcell.2020.00392

来源: DOAJ

【 摘 要 】

ObjectiveThe 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).Materials and MethodsstarBase 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.ResultsThe expression of CASC8 was observed to be high in 178 PAAD samples [fold change = 8.71, P = 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 in silico findings.ConclusionCASC8 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.

【 授权许可】

Unknown