本研究旨在利用生物信息学工具鉴定结直肠癌的生物标志物和分子因子，以有效地诊断和治疗此疾病。我们利用从GEO数据库检索到的数据序列，确定了与结直肠癌（CRC）相关的不同表达的基因（DEGs）。随后进行加权基因共表达网络分析（WGCNA）以探索与CRC诊断相关的共表达模块。接着，评估了综合模块与CRC阶段等临床特征之间的关系，并对所选定的模块基因进行了其他下游分析。 本研究在执行WGCNA方法后，选择了一个名为“蓝色模块”的模块，该模块与CRC阶段更显著相关，用于进一步评估。之后，通过Cytoscape评估所构建的154个蓝色模块基因的蛋白质-蛋白质相互作用网络时确定了八个中心基因。在这八个中心基因中，MMP9、SERPINH1、COL1A2、COL5A2、COL1A1、SPARC和COL5A1在CRC中的上调已在其他微阵列和TCGA数据中得到验证。根据mRNA-miRNA相互作用网络的结果，发现SERPINH1是miR-940的靶基因。最后，DGIDB数据库的结果表明，Andecaliximab、羧化葡萄糖胺、Marimastat、Tozuleristide、S-3304、Incyclinide、姜黄素、Prinomastat、Demethylwedelolactone和Bevacizumab等可作为治疗MMP9的靶向治疗药物。此外，Ocriplasmin和Collagenase clostridium histolyticum可靶向COL1A1、COL1A2、COL5A1和COL5A2。 综合本研究的结果表明，结直肠癌中七个中心基因（COL1A2、COL5A1、COL5A2、SERPINH1、MMP9、SPARC和COL1A1）的上调可作为CRC的诊断和进展生物标志物。另一方面，靶向SERPINH1的miR-940可作为CRC的潜在生物标志物。此外，Andecaliximab、羧化葡萄糖胺、Marimastat、Tozuleristide、S-3304、Incyclinide、姜黄素、Prinomastat、Demethylwedelolactone、Bevacizumab、Ocriplasmin以及Collagenase clostridium histolyticum被引入为CRC的治疗剂，其治疗潜力应通过实验评估。 Copyright © 2023 Elsevier Ltd. All rights reserved.

The purpose of this study was using bioinformatics tools to identify biomarkers and molecular factors involved in the diagnosis of colorectal cancer, which are effective for the diagnosis and treatment of the disease.We determined differentially expressed genes (DEGs) related to colorectal cancer (CRC) using the data series retrieved from GEO database. Then the weighted gene co-expression network analysis (WGCNA) was conducted to explore co-expression modules related to CRC diagnosis. Next, the relationship between the integrated modules with clinical features such as the stage of CRC was evaluated. Other downstream analyses were performed on selected module genes.In this study, after performing the WGCNA method, a module named blue module which was more significantly associated with the CRC stage was selected for further evaluation. Afterward, the Protein-protein interaction network through sting software for 154 genes of the blue module was constructed and eight hub genes were identified through the evaluation of constructed network with Cytoscape. Among these eight hub genes, upregulation of MMP9, SERPINH1, COL1A2, COL5A2, COL1A1, SPARC, and COL5A1 in CRC was validated in other microarray and TCGA data. Based on the results of the mRNA-miRNA interaction network, SERPINH1 was found as a target gene of miR-940. Finally, results of the DGIDB database indicated that Andecaliximab, Carboxylated glucosamine, Marimastat, Tozuleristide, S-3304, Incyclinide, Curcumin, Prinomastat, Demethylwedelolactone, and Bevacizumab, could be used as a therapeutic agent for targeting the MMP9. Furthermore, Ocriplasmin and Collagenase clostridium histolyticum could target COL1A1, COL1A2, COL5A1, and COL5A2.Taken together, the results of the current study indicated that seven hub genes including COL1A2, COL5A1, COL5A2, SERPINH1, MMP9, SPARC, and COL1A1 which were upregulated in CRC could be used as a diagnostic and progression biomarker of CRC. On the other hand, miR-940 which targets SERPINH1 could be used as a potential biomarker of CRC. More ever, Andecaliximab, Carboxylated glucosamine, Marimastat, Tozuleristide, S-3304, Incyclinide, Curcumin, Prinomastat, Demethylwedelolactone, Bevacizumab, Ocriplasmin , and Collagenase clostridium histolyticum were introduced as therapeutic agents for CRC which their therapeutic potential should be evaluated experimentally.Copyright © 2023 Elsevier Ltd. All rights reserved.