SOX9, miR-495, miR-590-3p, and miR-320d were identified as chemoradiotherapy-sensitive genes and miRNAs in colorectal cancer patients based on a microarray dataset

Binbin Du, Tao Wang, Xiongfei Yang, Jiankai Wang, Xinlong Shi, Xiaoying Wang, Dewang Wu, Lili Feng, Lingjuan Chen,  Weisheng Zhang

Abstract:

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.