Sun YuanLin, Liu Bin, Chen YuJia, Xing YanPeng, Zhang Yang
Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun, China.
Front Cell Dev Biol. 2022 Feb 11;9:811957. doi: 10.3389/fcell.2021.811957. eCollection 2021.
The potential biological processes and laws of the biological components in malignant tumors can be understood more systematically and comprehensively through multi-omics analysis. This study elaborately explored the role of lipid metabolism in the prognosis of colorectal cancer (CRC) from the metabonomics and transcriptomics. We performed K-means unsupervised clustering algorithm and t test to identify the differential lipid metabolites determined by liquid chromatography tandem mass spectrometry (LC-MS/MS) in the serum of 236 CRC patients of the First Hospital of Jilin University (JLUFH). Cox regression analysis was used to identify prognosis-associated lipid metabolites and to construct multi-lipid-metabolite prognostic signature. The composite nomogram composed of independent prognostic factors was utilized to individually predict the outcome of CRC patients. Glycerophospholipid metabolism was the most significant enrichment pathway for lipid metabolites in CRC, whose related hub genes (GMRHGs) were distinguished by gene set variation analysis (GSVA) and weighted gene co-expression network analysis (WGCNA). Cox regression and least absolute shrinkage and selection operator (LASSO) regression analysis were utilized to develop the prognostic signature. Six-lipid-metabolite and five-GMRHG prognostic signatures were developed, indicating favorable survival stratification effects on CRC patients. Using the independent prognostic factors as variables, we established a composite nomogram to individually evaluate the prognosis of CRC patients. The AUCs of one-, three-, and five-year ROC curves were 0.815, 0.815, and 0.805, respectively, showing auspicious prognostic accuracy. Furthermore, we explored the potential relationship between tumor microenvironment (TME) and immune infiltration. Moreover, the mutational frequency of TP53 in the high-risk group was significantly higher than that in the low-risk group ( < 0.001), while in the coordinate mutational status of TP53, the overall survival of CRC patients in the high-risk group was significantly lower than that in low-risk group with statistical differences. We identified the significance of lipid metabolism for the prognosis of CRC from the aspects of metabonomics and transcriptomics, which can provide a novel perspective for promoting individualized treatment and revealing the potential molecular biological characteristics of CRC. The composite nomogram including a six-lipid-metabolite prognostic signature is a promising predictor of the prognosis of CRC patients.
通过多组学分析，可以更系统、全面地了解恶性肿瘤中生物成分的潜在生物学过程和规律。本研究从代谢组学和转录组学角度，精心探究了脂质代谢在结直肠癌（CRC）预后中的作用。我们对吉林大学第一医院（JLUFH）236例CRC患者的血清进行液相色谱串联质谱（LC-MS/MS）检测，运用K均值无监督聚类算法和t检验来识别差异脂质代谢物。采用Cox回归分析来确定与预后相关的脂质代谢物，并构建多脂质代谢物预后特征。由独立预后因素组成的综合列线图用于个体预测CRC患者的预后。甘油磷脂代谢是CRC中脂质代谢物最显著的富集途径，通过基因集变异分析（GSVA）和加权基因共表达网络分析（WGCNA）来区分其相关的枢纽基因（GMRHGs）。利用Cox回归和最小绝对收缩和选择算子（LASSO）回归分析来构建预后特征。开发了六脂质代谢物和五GMRHG预后特征，对CRC患者显示出良好的生存分层效果。以独立预后因素为变量，我们建立了一个综合列线图来个体评估CRC患者的预后。1年、3年和5年ROC曲线的AUC分别为0.815、0.815和0.805，显示出良好的预后准确性。此外，我们还探究了肿瘤微环境（TME）与免疫浸润之间的潜在关系。而且，高危组中TP53的突变频率显著高于低危组（<0.001），而在TP53的协同突变状态下，高危组CRC患者的总生存期显著低于低危组，具有统计学差异。我们从代谢组学和转录组学方面确定了脂质代谢对CRC预后的意义，这可为促进个体化治疗和揭示CRC潜在的分子生物学特征提供新的视角。包含六脂质代谢物预后特征的综合列线图是CRC患者预后的一个有前景的预测指标。
