Wang Zhiyu, Zhang Zhuoqi, Zhang Ke, Zhou Qiaoxia, Chen Sidong, Zheng Hao, Wang Guoqiang, Cai Shangli, Wang Fujing, Li Shenglong
Department of Medical Oncology, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Affiliated Hospital of Hebei University, Baoding, China.
Department of Gastrointestinal Surgery, Affiliated Hospital of Hebei University, Baoding, China.
Front Oncol. 2022 May 5;12:881953. doi: 10.3389/fonc.2022.881953. eCollection 2022.
Glycerolipid metabolism is involved in the genesis and progression of colon cancer. The current study aims at exploring the prognostic value and potential molecular mechanism of glycerolipid metabolism-related genes in colon cancer from the perspective of multi-omics.
Clinical information and mRNA expression data of patients with colon cancer were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Single-sample gene set enrichment analysis (ssGSEA) was applied to calculate the glycerolipid metabolism-related gene enrichment score (GLMS). Univariable and multivariable Cox regression analyses were used to study the prognostic value of GLMS in TCGA-COAD and GSE39582 cohorts. The molecular mechanism of the prognostic factor was investigated immune cell infiltration estimation and correlation analysis of cancer hallmark pathways. Single-cell transcriptomic dataset GSE146771 was used to identify the cell populations which glycerolipid metabolism targeted on.
The GLMS was found to be associated with tumor location and consensus molecular types (CMSs) of colon cancer in TCGA-COAD cohort ( < 0.05). Patients in the low-GLMS group exhibited poorer overall survival (OS) in TCGA cohort ( = 0.03; HR, 0.63; 95% CI, 0.42-0.94), which was further validated in the GSE39582 dataset ( < 0.001; HR, 0.57; 95% CI, 0.43-0.76). The association between the GLMS and OS remained significant in the multivariable analysis (TCGA cohort: = 0.04; HR, 0.64; 95% CI, 0.42-0.98; GSE39582 cohort: < 0.001; HR, 0.60; 95% CI, 0.45-0.80). The GLMS was positively correlated with cancer hallmark pathways including bile acid metabolism, xenobiotic metabolism, and peroxisome and negatively correlated with pathways such as interferon gamma response, allograft rejection, apoptosis, and inflammatory response ( < 0.05). Increased immune infiltration and upregulated expression of immune checkpoints were observed in patients with lower GLMS ( < 0.05). Single-cell datasets verified the different distribution of GLMS in cell subsets, with significant enrichment of GLMS in malignant cells and Tprolif cells.
We demonstrated that GLMS was a potential independent prognostic factor for colon cancer. The GLMS was also correlated with several cancer hallmark pathways, as well as immune microenvironment.
甘油脂质代谢参与结肠癌的发生和发展。本研究旨在从多组学角度探讨甘油脂质代谢相关基因在结肠癌中的预后价值及潜在分子机制。
从癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）获取结肠癌患者的临床信息和mRNA表达数据。应用单样本基因集富集分析（ssGSEA）计算甘油脂质代谢相关基因富集评分（GLMS）。采用单因素和多因素Cox回归分析研究GLMS在TCGA-COAD和GSE39582队列中的预后价值。通过免疫细胞浸润估计和癌症特征通路的相关性分析研究预后因素的分子机制。使用单细胞转录组数据集GSE146771鉴定甘油脂质代谢靶向的细胞群体。
在TCGA-COAD队列中发现GLMS与结肠癌的肿瘤位置和共识分子类型（CMSs）相关（<0.05）。在TCGA队列中，低GLMS组患者的总生存期（OS）较差（=0.03；HR，0.63；95%CI，0.42-0.94），这在GSE39582数据集中得到进一步验证（<0.001；HR，0.57；95%CI，0.43-0.76）。在多因素分析中，GLMS与OS之间的关联仍然显著（TCGA队列：=0.04；HR，0.64；95%CI，0.42-0.98；GSE39582队列：<0.001；HR，0.60；95%CI，0.45-0.80）。GLMS与包括胆汁酸代谢、异源物质代谢和过氧化物酶体在内的癌症特征通路呈正相关，与干扰素γ反应、同种异体移植排斥、凋亡和炎症反应等通路呈负相关（<0.05）。在低GLMS患者中观察到免疫浸润增加和免疫检查点表达上调（<0.05）。单细胞数据集验证了GLMS在细胞亚群中的不同分布，GLMS在恶性细胞和Tprolif细胞中显著富集。
我们证明GLMS是结肠癌潜在的独立预后因素。GLMS还与多种癌症特征通路以及免疫微环境相关。
