Biomarker detection is one of the most important and challenging problems in cancer studies. Recently, non-coding RNA based biomarkers such as miRNA expression levels have been used for early diagnosis of many cancer types. In this study, a systems biology approach was used to detect novel miRNA based biomarkers for CRC diagnosis in early stages. The mRNA expression data from three CRC stages (Low-grade Intraepithelial Neoplasia (LIN), High-grade Intraepithelial Neoplasia (HIN) and Adenocarcinoma) were used to reconstruct co-expression networks. The networks were clustered to extract co-expression modules and detected low preserved modules among CRC stages. Then, the experimentally validated mRNA–miRNA interaction data were applied to reconstruct three mRNA–miRNA bipartite networks. Twenty miRNAs with the highest degree (hub miRNAs) were selected in each bipartite network to reconstruct three bipartite subnetworks for further analysis. The analysis of these hub miRNAs in the bipartite subnetworks revealed 30 distinct important miRNAs as prognostic markers in CRC stages. There are two novel CRC related miRNAs (hsa-miR-190a-3p and hsa-miR-1277-5p) in these 30 hub miRNAs that have not been previously reported in CRC. Furthermore, a drug–gene interaction network was reconstructed to detect potential candidate drugs for CRC treatment. Our analysis shows that the hub miRNAs in the mRNA–miRNA bipartite network are very essential in CRC progression and should be investigated precisely in future studies. In addition, there are many important target genes in the results that may be critical in CRC progression and can be analyzed as therapeutic targets in future research.

中文翻译：

---

mRNA-miRNA二分体网络重建可预测大肠癌分期的预后模块生物标志物

生物标志物检测是癌症研究中最重要和最具挑战性的问题之一。最近，基于非编码RNA的生物标记物（如miRNA表达水平）已用于多种癌症的早期诊断。在这项研究中，系统生物学方法被用来检测基于miRNA的新型生物标志物，以用于CRC的早期诊断。来自三个CRC阶段（低度上皮内瘤变（LIN），高等级上皮内瘤变（HIN）和腺癌）的mRNA表达数据被用于重建共表达网络。将网络聚类以提取共表达模块，并在CRC阶段中检测到低保留的模块。然后，将经过实验验证的mRNA-miRNA相互作用数据用于重建三个mRNA-miRNA双向网络。在每个二分网络中选择了二十个最高程度的miRNA（集线器miRNA），以重建三个二分子网，以进行进一步分析。在二分子网中对这些中枢miRNA的分析显示，有30种不同的重要miRNA作为CRC阶段的预后标志物。在这30种枢纽miRNA中，有两种新颖的CRC相关miRNA（hsa-miR-190a-3p和hsa-miR-1277-5p），以前尚未在CRC中报道。此外，重建了药物-基因相互作用网络以检测可能用于CRC治疗的候选药物。我们的分析表明，mRNA-miRNA双向网络中的中枢miRNA在CRC进展中非常重要，应在以后的研究中进行精确研究。此外，