结肠腺癌是死亡率最高的肿瘤之一,结肠腺癌的发生或发展是导致患者死亡的主要原因。然而,预测肿瘤进展的分子机制和生物标志物目前尚不清楚。为了了解肿瘤的分子机制和进展,我们利用TCGA数据库鉴定差异表达基因.在确定LGR4表达水平不同的结肠腺癌组织和正常组织之间的差异表达基因后,蛋白质-蛋白质相互作用,基因本体论,途径富集,基因集富集分析,免疫细胞浸润分析。这里,十大枢纽基因,即,ALB,F2,APOA2,CYP1A1,SPRR2B,APOA1、APOB、CYP3A4,SST,还有GCG,被确认,并进行相关分析。Kaplan-Meier分析显示,LGR4的高表达与结肠腺癌患者的总生存期相关。虽然LGR4在正常组织中的表达水平高于肿瘤组织。进一步的功能分析表明,LGR4在结肠腺癌中的高表达可能与上调代谢相关通路有关。例如,胆固醇生物合成途径。这些结果通过基因集富集分析得到证实。免疫细胞浸润分析清楚显示T细胞浸润百分率明显高于其他免疫细胞,和TIMER分析显示T细胞浸润和LGR4表达之间呈正相关。最后,COAD癌细胞,Caco-2用于与角鲨烯和25-羟基胆固醇-3-硫酸盐孵育,相关实验结果证实,胆固醇生物合成途径参与了COAD肿瘤发生的增殖调控。我们的研究表明,LGR4可以通过影响代谢相关途径成为结肠腺癌的新兴诊断和预后生物标志物。
Colon adenocarcinoma is one of the tumors with the highest mortality rate, and tumorigenesis or development of colon adenocarcinoma is the major reason leading to patient death. However, the molecular mechanism and biomarker to predict tumor progression are currently unclear. With the goal of understanding the molecular mechanism and tumor progression, we utilized the TCGA database to identify differentially expressed genes. After identifying the differentially expressed genes among colon adenocarcinoma tissues with different expression levels of LGR4 and normal tissue, protein-protein interaction, gene ontology, pathway enrichment, gene set enrichment analysis, and immune cell infiltration analysis were conducted. Here, the top 10 hub genes, i.e., ALB, F2, APOA2, CYP1A1, SPRR2B, APOA1, APOB, CYP3A4, SST, and GCG, were identified, and relative correlation analysis was conducted. Kaplan-Meier analysis revealed that higher expression of LGR4 correlates with overall survival of colon adenocarcinoma patients, although expression levels of LGR4 in normal tissues are higher than in tumor tissues. Further functional analysis demonstrated that higher expression of LGR4 in colon adenocarcinoma may be linked to up-regulate metabolism-related pathways, for example, the cholesterol biosynthesis pathway. These results were confirmed by gene set enrichment analysis. Immune cell infiltration analysis clearly showed that the infiltration percentage of T cells was significantly higher than other immune cells, and TIMER analysis revealed a positive correlation between T-cell infiltration and LGR4 expression. Finally, COAD cancer cells, Caco-2, were employed to be incubated with squalene and 25-hydroxycholesterol-3-sulfate, and relative experimental results confirmed that the cholesterol biosynthesis pathway involved in modulating the proliferation of COAD tumorigenesis. Our investigation revealed that LGR4 can be an emerging diagnostic and prognostic biomarker for colon adenocarcinoma by affecting metabolism-related pathways.