Department of Anorectal Surgery, Gansu Provincial Hospital, Lanzhou, China.
Department of Radiotherapy, Gansu Provincial Hospital, Lanzhou, China.
Neoplasma. 2019 Jan 15;66(1):8-19. doi: 10.4149/neo_2018_170324N214. Epub 2018 Aug 9.
The study aimed to identify chemoradiotherapy (CRT)-sensitive biomarkers in colorectal cancer (CRC) patients. The GSE15781 dataset used in this study contains 42 samples: 22 CRC tissues (non-CRT: n = 13; CRT: n = 9) and 20 normal colorectal tissues (non-CRT: n = 10; CRT: n = 10). Following pretreatment, differentially expressed genes were selected using the limma package. Potential CRT-sensitive genes were identified with Venn analysis and then enriched in function and pathway clusters using the DAVID online tool. Moreover, protein-protein interaction (PPI) network analysis was implemented using the STRING database. The TRRUST database was used to establish a transcription factor (TF)-target transcriptional network. A miRNA-mRNA network was constructed based on relevant databases. miRNA and mRNA expression levels were analyzed using real-time quantitative PCR. A group of 259 candidate CRT-sensitive genes were identified that were mainly enriched in cell cycle regulation, adhesion-associated processes, and the p53 signaling pathway. A PPI network was established that contained striking nodes, including ITGA2, MYC, ESR1, and dihydropyrimidine dehydrogenase (DPYD), among which ESR1 was linked to MYC, and the two nodes were also highlighted in the TF-target regulation network. SRY-box 9 (SOX9) was another key TF. Hsa-miR-590-3p, hsa-miR-495, hsa-miR-320c, and hsa-miR-320d were predominant in the miRNA-mRNA network. Expression levels of SOX9, DPYD mRNA, miR-495, and miR-590-3p were clearly reduced after X-ray treatment in irradiated HT-29 cells, whereas that of miR-320d was notably enhanced. SOX9 may be a CRT-sensitive gene in CRC patients, and hsa-miR-590-3p, hsa-miR-495, and hsa-miR-320d may be CRT-sensitive microRNAs in CRC patients. Therefore, SOX9, hsa-miR-590-3p, hsa-miR-495, and hsa-miR-320d may be used as sensitive biomarkers in CRC patients.
本研究旨在鉴定结直肠癌(CRC)患者的放化疗(CRT)敏感生物标志物。本研究使用的 GSE15781 数据集包含 42 个样本:22 个 CRC 组织(非 CRT:n=13;CRT:n=9)和 20 个正常结直肠组织(非 CRT:n=10;CRT:n=10)。预处理后,使用 limma 包选择差异表达基因。通过 Venn 分析鉴定潜在的 CRT 敏感基因,然后使用 DAVID 在线工具富集功能和途径聚类。此外,使用 STRING 数据库进行蛋白质-蛋白质相互作用(PPI)网络分析。使用 TRRUST 数据库建立转录因子(TF)-靶转录网络。基于相关数据库构建 miRNA-mRNA 网络。使用实时定量 PCR 分析 miRNA 和 mRNA 的表达水平。鉴定出一组 259 个候选 CRT 敏感基因,主要富集在细胞周期调控、粘附相关过程和 p53 信号通路中。建立了一个包含 ITGA2、MYC、ESR1 和二氢嘧啶脱氢酶(DPYD)等显著节点的 PPI 网络,其中 ESR1 与 MYC 相关,两个节点也在 TF-靶调控网络中突出显示。SRY-box 9(SOX9)是另一个关键 TF。hsa-miR-590-3p、hsa-miR-495、hsa-miR-320c 和 hsa-miR-320d 在 miRNA-mRNA 网络中占主导地位。X 射线处理后,照射 HT-29 细胞中 SOX9、DPYD mRNA、miR-495 和 miR-590-3p 的表达水平明显降低,而 miR-320d 的表达水平明显增强。SOX9 可能是 CRC 患者的 CRT 敏感基因,hsa-miR-590-3p、hsa-miR-495 和 hsa-miR-320d 可能是 CRC 患者的 CRT 敏感 microRNA。因此,SOX9、hsa-miR-590-3p、hsa-miR-495 和 hsa-miR-320d 可用作 CRC 患者的敏感生物标志物。