Department of Geriatric Surgery, Xiangya Hospital, Central South University, Changsha 410008, China.
Department of Pancreatobiliary Surgery, Xiangya Hospital, Central South University, Changsha 410008, China.
Acta Biochim Pol. 2022 Jun 8;69(2):327-333. doi: 10.18388/abp.2020_5758.
This study aimed to identify novel prognostic biomarkers of pancreatic ductal adenocarcinoma (PDAC) using bioinformatics analyzes.
Clinical information, microRNAs (miRNAs), and genes expression profile data from PDAC cases were downloaded from the Cancer Genome Atlas (TCGA) database. The potential prognostic risk miRNAs and genes were screened using the Elastic Net Cox proportional risk regression hazards (EN-COX) model. The receiver operating characteristic (ROC) curve and the Kaplan-Meier (KM) curve were used to identify miRNAs and genes of significant prognostic risk. Furthermore, significant prognostic risk miRNAs were functional enrichment analyses based on their target genes. Furthermore, the survival analyzes of the hub genes were validated through OncoLnc.
Complete clinical records and expression data of 797 miRNAs and 19969 genes from 137 PDAC cases were obtained, of which 59 potential prognostic risk factors, including 54 genes and 5 miRNAs, were selected by EN-COX analyzes. A total of 17 significant prognostic risk markers were identified (all P<0.05), including 16 genes and 1 miRNA (miRNA-125a). The miRNA-125a target genes were found in the MiRWalk database and the function enrichment analyzes were performed in the the DAVID website. Furthermore, according to data from the Oncomine and Human Protein Atlas (HPA) databases, the mRNA and protein level of frizzled class receptor 8 (FZD8) were overexpressed in pancreatic cancer tissues compared to the corresponding noncancer normal tissues (P<0.001). However, both glutathione S-transferase mu 4 (GSTM4) and inducible T cell costimulator ligand (ICOSLG) were negatively regulated in tissues of pancreatic cancer tissues (P<0.001). Finally, survival analysis was used to validate these factors by the OncoLnc database, and the results revealed that overexpression of ICOSLG was associated with a better prognosis (P=0.025).
This study showed that the expression levels of FZD8, GSTM4 and ICOSLG were significantly different between PDAC and non-tumor tissues, especially ICOSLG, which could be a prognostic indicator and therapeutic target for PDAC.
本研究旨在使用生物信息学分析方法，鉴定胰腺导管腺癌（PDAC）的新型预后生物标志物。
从癌症基因组图谱（TCGA）数据库中下载 PDAC 病例的临床信息、微小 RNA（miRNA）和基因表达谱数据。使用弹性网络 Cox 比例风险回归风险（EN-COX）模型筛选潜在的预后风险 miRNA 和基因。使用接收器工作特征（ROC）曲线和 Kaplan-Meier（KM）曲线识别具有显著预后风险的 miRNA 和基因。此外，根据其靶基因对显著预后风险的 miRNA 进行功能富集分析。此外，通过 OncoLnc 验证了枢纽基因的生存分析。
从 137 例 PDAC 病例中获得了完整的临床记录和 797 个 miRNA 和 19969 个基因的表达数据，其中通过 EN-COX 分析筛选出 59 个潜在的预后风险因素，包括 54 个基因和 5 个 miRNA。总共鉴定出 17 个显著的预后风险标志物（均 P<0.05），包括 16 个基因和 1 个 miRNA（miRNA-125a）。在 MiRWalk 数据库中找到了 miRNA-125a 的靶基因，并在 DAVID 网站上进行了功能富集分析。此外，根据 Oncomine 和人类蛋白质图谱（HPA）数据库的数据，与相应的非癌正常组织相比，胰腺癌细胞组织中 frizzled 类受体 8（FZD8）的 mRNA 和蛋白水平过度表达（P<0.001）。然而，谷胱甘肽 S-转移酶 mu 4（GSTM4）和诱导型 T 细胞共刺激配体（ICOSLG）在胰腺癌细胞组织中均受到负调节（P<0.001）。最后，通过 OncoLnc 数据库对这些因素进行了生存分析验证，结果表明 ICOSLG 的过表达与更好的预后相关（P=0.025）。
本研究表明，FZD8、GSTM4 和 ICOSLG 在 PDAC 与非肿瘤组织之间的表达水平存在显著差异，尤其是 ICOSLG，它可能是 PDAC 的预后指标和治疗靶点。
