PLOD3:一种潜在的直肠癌预后生物标志物

PLOD3:A potential novel prognostic biomarker for rectal cancer

目的:探讨PLOD3在直肠癌中的生物学功能及预后价值。方法:GEPIA2、GENT2、TIMER、HPA、K-M Plot、cBioPortal、UALCAN、NetworkAnalys、GeneMANIA、Metascape、DAVID和SurvivalMeth用于分析PLOD3基因在直肠癌中的预后价值和生物学功能。结果:与正常直肠组织相比,直肠癌中PLOD3基因的mRNA和蛋白呈显著高表达状态。高表达PLOD3与直肠癌患者较短的总生存期(OS)显著相关。PLOD3的表达水平与肿瘤免疫浸润细胞CD8^(+)T呈负相关。基因突变分析结果显示直肠癌患者中PLOD3基因突变率约为10%。K-M生存分析发现在肿瘤突变负荷(TMB)高危组中,PLOD3的mRNA高表达与直肠癌患者较短的OS显著相关。功能富集分析(KEGG、GO)显示直肠癌中PLOD3的生物学功能主要包括蛋白质羟基化、胶原蛋白生物合成和修饰酶、赖氨酸降解、细胞修饰氨基酸代谢过程、脂肪酸氧化。直肠癌组织中PLOD3甲基化水平较对照组显著降低,高危组患者甲基化水平显著降低,高危组与较短的OS显著相关。结论:PLOD3是直肠癌预后新的生物标志物,为直肠癌的诊断、寻找潜在治疗靶点、个体化治疗及预后评估提供参考。

Objective:To investigate the prognostic and biological functions of PLOD3 in rectal cancer.Methods:GEPIA2,GENT2,TIMER,HPA,K-M Plot,cBioPortal,UALCAN,NetworkAnalys,GeneMANIA,Metascape,DAVID and SurvivalMeth were used to analyze the prognostic value and biological function of PLOD3 gene in rectal cancer.Results:Compared with normal rectal tissue,the mRNA and protein expressions of PLOD3 in rectal cancer were significantly higher.High expression of PLOD3 was significantly associated with poor overall survival(OS)in patients with rectal cancer.The expression level of PLOD3 was negatively correlated with CD8^(+)T cells.The results of gene mutation analysis showed significant PLOD3 gene changes(10%)in patients with rectal cancer,and K-M survival analysis found that in the high-risk group of tumor mutational burden(TMB),higher mRNA expression of PLOD3 was significantly associated with shorter OS in patients with rectal cancer.Through functional enrichment analysis(KEGG,GO),it was found that the biological function of PLOD3 in rectal cancer mainly include protein hydroxylation,collagen biosynthesis and modification enzymes,lysine degradation,cellular modification of amino acid metabolism,and fatty acid oxidation.The results of methylation analysis showed that the methylation level of PLOD3 in patients with rectal cancer was significantly lower than that in control group.The methylation level of patients in high-risk group decreased significantly,and the high-risk group was significantly related to the shorter OS.Conclusion:PLOD3 is a new biomarker for the prognosis of rectal cancer,which provide evidence and new sights for the diagnosis,potential therapeutic targets,individualized treatment and prognostic assessment of rectal cancer patients.