Lipid Metabolism-Related Gene Markers Used for Prediction Prognosis, Immune Microenvironment, and Tumor Stage of Pancreatic Cancer

IF 2.1 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yuan Shu, Haiqiang Huang, Minjie Gao, Wenjie Xu, Xiang Cao, Xiaoze Jia, Bo Deng
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引用次数: 0

Abstract

Recently, more and more evidence shows that lipid metabolism disorder has been observed in tumor, which impacts tumor cell proliferation, survival, invasion, metastasis, and response to the tumor microenvironment (TME) and tumor treatment. However, hitherto there has not been sufficient research to demonstrate the role of lipid metabolism in pancreatic cancer. This study contrives to get an insight into the relationship between the characteristics of lipid metabolism and pancreatic cancer. We collected samples of patients with pancreatic cancer from the Gene Expression Omnibus (GEO), the Therapeutically Applicable Research to Generate Effective Treatments (TARGET), and the International Cancer Genome Consortium (ICGC) databases. Firstly, we implemented univariate regression analysis to get prognosis-related lipid metabolism genes screened and a construction of protein–protein interaction (PPI) network ensued. Then, contingent on our screening results, we explored the molecular subtypes mediated by lipid metabolism-related genes and the correlated TME cell infiltration. Additionally, we studied the disparately expressed genes among disparate lipid metabolism subtypes and established a scoring model of lipid metabolism-related characteristics using the least absolute shrinkage and selection operator (LASSO) regression analysis. At last, we explored the relationship between the scoring model and disease prognosis, tumor stage, tumor microenvironment, and immunotherapy. Two subtypes, C1 and C2, were identified, and lipid metabolism-related genes were studied. The result indicated that the patients with subtype C2 have a significantly lower survival rate than that of the patients with subtype C1, and we found difference in abundance of different immune-infiltrating cells. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed the association of these differentially expressed genes with functions and pathways related to lipid metabolism. Finally, we established a scoring model of lipid metabolism-related characteristics based on the disparately expressed genes. The results show that our scoring model have a substantial effect on forecasting the prognosis of patients with pancreatic cancer. The lipid metabolism model is an important biomarker of pancreatic cancer. Using the model, the relationship between disease prognosis, molecular subtypes, TME cell infiltration characteristics, and immunotherapy in pancreatic cancer patients could be explored.

用于预测胰腺癌预后、免疫微环境和肿瘤分期的脂质代谢相关基因标记物
近来,越来越多的证据表明,肿瘤中出现了脂质代谢紊乱,而脂质代谢紊乱会影响肿瘤细胞的增殖、生存、侵袭、转移以及对肿瘤微环境(TME)和肿瘤治疗的反应。然而,迄今为止还没有足够的研究证明脂质代谢在胰腺癌中的作用。本研究试图深入了解脂质代谢特征与胰腺癌之间的关系。我们从基因表达总库(Gene Expression Omnibus,GEO)、有效治疗研究(Therapeutically Applicable Research to Generate Effective Treatments,TARGET)和国际癌症基因组联盟(International Cancer Genome Consortium,ICGC)数据库中收集了胰腺癌患者样本。首先,我们通过单变量回归分析筛选出与预后相关的脂质代谢基因,并构建了蛋白质相互作用(PPI)网络。然后,根据筛选结果,我们探讨了脂质代谢相关基因介导的分子亚型以及相关的TME细胞浸润。此外,我们还研究了不同脂质代谢亚型中的差异表达基因,并利用最小绝对收缩和选择算子(LASSO)回归分析建立了脂质代谢相关特征的评分模型。最后,我们探讨了评分模型与疾病预后、肿瘤分期、肿瘤微环境和免疫疗法之间的关系。我们确定了 C1 和 C2 两种亚型,并对脂质代谢相关基因进行了研究。结果表明,C2亚型患者的生存率明显低于C1亚型患者,而且我们发现不同免疫浸润细胞的丰度存在差异。基因本体(GO)和京都基因组百科全书(KEGG)通路富集分析显示,这些差异表达基因与脂质代谢相关的功能和通路有关。最后,我们根据差异表达基因建立了脂质代谢相关特征的评分模型。结果表明,我们的评分模型对预测胰腺癌患者的预后有很大作用。脂质代谢模型是胰腺癌的重要生物标志物。利用该模型,可以探索胰腺癌患者的疾病预后、分子亚型、TME细胞浸润特征和免疫疗法之间的关系。
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来源期刊
Biochemical Genetics
Biochemical Genetics 生物-生化与分子生物学
CiteScore
3.90
自引率
0.00%
发文量
133
审稿时长
4.8 months
期刊介绍: Biochemical Genetics welcomes original manuscripts that address and test clear scientific hypotheses, are directed to a broad scientific audience, and clearly contribute to the advancement of the field through the use of sound sampling or experimental design, reliable analytical methodologies and robust statistical analyses. Although studies focusing on particular regions and target organisms are welcome, it is not the journal’s goal to publish essentially descriptive studies that provide results with narrow applicability, or are based on very small samples or pseudoreplication. Rather, Biochemical Genetics welcomes review articles that go beyond summarizing previous publications and create added value through the systematic analysis and critique of the current state of knowledge or by conducting meta-analyses. Methodological articles are also within the scope of Biological Genetics, particularly when new laboratory techniques or computational approaches are fully described and thoroughly compared with the existing benchmark methods. Biochemical Genetics welcomes articles on the following topics: Genomics; Proteomics; Population genetics; Phylogenetics; Metagenomics; Microbial genetics; Genetics and evolution of wild and cultivated plants; Animal genetics and evolution; Human genetics and evolution; Genetic disorders; Genetic markers of diseases; Gene technology and therapy; Experimental and analytical methods; Statistical and computational methods.
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