{"title":"Identification of lipid metabolism-related marker genes in colorectal cancer.","authors":"Bo Gao, Jitao Hu, Hao Wu, Baokun Li","doi":"10.62347/EGUX7327","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To identify lipid metabolism associated biomarkers in colorectal cancer (CRC).</p><p><strong>Methods: </strong>To refine our list of candidate genes, we utilized the Molecular Complex Detection (MCODE) plug-in within Cytoscape software and performed protein-protein interaction (PPI) network analysis to extract hub genes centrally located within the networks, which potentially possess important regulatory functions. Hub gene-associated miRNAs and transcription factors (TFs) were analyzed using miRNet. Immunohistochemical staining was employed to verify the expression levels of hub genes in clinical CRC tissues. Concurrently, cellular experiments were designed to explore the functional roles of the hub gene DHCR7 at the cellular level, providing scientific evidence for the precision treatment of CRC.</p><p><strong>Results: </strong>A total of 9008 differentially expressed genes (DEGs) were identified between CRC and control samples. Gene Set Enrichment Analysis (GSEA) revealed that these DEGs were mainly enriched in biological processes such as myogenesis, adipogenesis, oxidative phosphorylation, and fatty acid metabolism. Using Weighted Gene Co-expression Network Analysis (WGCNA), we found that the pink and yellow modules were most significantly associated with CRC. Cytoscape analysis identified six hub genes (DHCR7, FABP4, FASN, FAXDC2, PTGIS, SLC27A6). Their diagnostic performance was verified in the external GSE23878 dataset. Clinical studies showed a downregulation trend in the expression of FAXDC2 and PTGIS in CRC tissue samples, while FASN and DHCR7 were up-regulated in colon cancer tissues. However, the expression trend of FABP4 was inconsistent with previous bioinformatics predictions. Further cellular experimental results demonstrated that DHCR7 knockdown significantly inhibited CRC cell proliferation and induced apoptosis, which strongly supported the previous bioinformatics analysis.</p><p><strong>Conclusion: </strong>Our research successfully identified six hub genes in CRC through a series of rigorous analyses and experimental validations. These findings provide important molecular basis for further investigation into the pathogenesis and progression of CRC.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 5","pages":"2022-2040"},"PeriodicalIF":2.9000,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163457/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of cancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.62347/EGUX7327","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objective: To identify lipid metabolism associated biomarkers in colorectal cancer (CRC).
Methods: To refine our list of candidate genes, we utilized the Molecular Complex Detection (MCODE) plug-in within Cytoscape software and performed protein-protein interaction (PPI) network analysis to extract hub genes centrally located within the networks, which potentially possess important regulatory functions. Hub gene-associated miRNAs and transcription factors (TFs) were analyzed using miRNet. Immunohistochemical staining was employed to verify the expression levels of hub genes in clinical CRC tissues. Concurrently, cellular experiments were designed to explore the functional roles of the hub gene DHCR7 at the cellular level, providing scientific evidence for the precision treatment of CRC.
Results: A total of 9008 differentially expressed genes (DEGs) were identified between CRC and control samples. Gene Set Enrichment Analysis (GSEA) revealed that these DEGs were mainly enriched in biological processes such as myogenesis, adipogenesis, oxidative phosphorylation, and fatty acid metabolism. Using Weighted Gene Co-expression Network Analysis (WGCNA), we found that the pink and yellow modules were most significantly associated with CRC. Cytoscape analysis identified six hub genes (DHCR7, FABP4, FASN, FAXDC2, PTGIS, SLC27A6). Their diagnostic performance was verified in the external GSE23878 dataset. Clinical studies showed a downregulation trend in the expression of FAXDC2 and PTGIS in CRC tissue samples, while FASN and DHCR7 were up-regulated in colon cancer tissues. However, the expression trend of FABP4 was inconsistent with previous bioinformatics predictions. Further cellular experimental results demonstrated that DHCR7 knockdown significantly inhibited CRC cell proliferation and induced apoptosis, which strongly supported the previous bioinformatics analysis.
Conclusion: Our research successfully identified six hub genes in CRC through a series of rigorous analyses and experimental validations. These findings provide important molecular basis for further investigation into the pathogenesis and progression of CRC.
目的：鉴定结直肠癌（CRC）中脂质代谢相关生物标志物。方法：为了完善我们的候选基因列表，我们利用Cytoscape软件中的分子复合物检测（MCODE）插件，并进行蛋白质-蛋白质相互作用（PPI）网络分析，提取位于网络中心的枢纽基因，这些基因可能具有重要的调控功能。使用miRNet分析枢纽基因相关mirna和转录因子（tf）。采用免疫组化染色法验证临床结直肠癌组织中枢纽基因的表达水平。同时，设计细胞实验，探索枢纽基因DHCR7在细胞水平上的功能作用，为CRC的精准治疗提供科学依据。结果：在结直肠癌和对照组之间共鉴定出9008个差异表达基因（DEGs）。基因集富集分析（Gene Set Enrichment Analysis， GSEA）显示，这些deg主要富集于肌生成、脂肪生成、氧化磷酸化和脂肪酸代谢等生物过程中。使用加权基因共表达网络分析（WGCNA），我们发现粉色和黄色模块与CRC的相关性最显著。细胞景观分析鉴定出6个枢纽基因（DHCR7、FABP4、FASN、FAXDC2、PTGIS、SLC27A6）。在外部GSE23878数据集中验证了它们的诊断性能。临床研究显示FAXDC2和PTGIS在结直肠癌组织样本中表达下调，而FASN和DHCR7在结肠癌组织中表达上调。然而，FABP4的表达趋势与之前的生物信息学预测不一致。进一步的细胞实验结果表明，DHCR7敲低显著抑制CRC细胞增殖并诱导凋亡，这有力地支持了之前的生物信息学分析。结论：通过一系列严格的分析和实验验证，我们的研究成功地鉴定了CRC中的6个枢纽基因。这些发现为进一步研究结直肠癌的发病机制和进展提供了重要的分子基础。
期刊介绍：
The American Journal of Cancer Research (AJCR) (ISSN 2156-6976), is an independent open access, online only journal to facilitate rapid dissemination of novel discoveries in basic science and treatment of cancer. It was founded by a group of scientists for cancer research and clinical academic oncologists from around the world, who are devoted to the promotion and advancement of our understanding of the cancer and its treatment. The scope of AJCR is intended to encompass that of multi-disciplinary researchers from any scientific discipline where the primary focus of the research is to increase and integrate knowledge about etiology and molecular mechanisms of carcinogenesis with the ultimate aim of advancing the cure and prevention of this increasingly devastating disease. To achieve these aims AJCR will publish review articles, original articles and new techniques in cancer research and therapy. It will also publish hypothesis, case reports and letter to the editor. Unlike most other open access online journals, AJCR will keep most of the traditional features of paper print that we are all familiar with, such as continuous volume, issue numbers, as well as continuous page numbers to retain our comfortable familiarity towards an academic journal.
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