Liu Ge-Liang, Chen Xi-Meng, Zhang Jun-Dong, Chen Hao-Ran, Wang Zi-Ning, Zhi Peng, Li Zhuo-Yang, He Pei-Feng, Lu Xue-Chun
Management School of Shanxi Medical University;Taiyuan 030001, Shanxi Province, China.Shanxi Key Laboratory of Big Data for Clinical Decision Research, Taiyuan 030001, Shanxi Province, China.
Department of Hematology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing 100853, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2023 Feb;31(1):162-169. doi: 10.19746/j.cnki.issn.1009-2137.2023.01.026.
To screen the prognostic biomarkers of metabolic genes in patients with multiple myeloma (MM), and construct a prognostic model of metabolic genes.
The histological database related to MM patients was searched. Data from MM patients and healthy controls with complete clinical information were selected for analysis.The second generation sequencing data and clinical information of bone marrow tissue of MM patients and healthy controls were collected from human protein atlas (HPA) and multiple myeloma research foundation (MMRF) databases. The gene set of metabolism-related pathways was extracted from Molecular Signatures Database (MSigDB) by Perl language. The biomarkers related to MM metabolism were screened by difference analysis, univariate Cox risk regression analysis and LASSO regression analysis, and the risk prognostic model and Nomogram were constructed. Risk curve and survival curve were used to verify the grouping effect of the model. Gene set enrichment analysis (GSEA) was used to study the difference of biological pathway enrichment between high risk group and low risk group. Multivariate Cox risk regression analysis was used to verify the independent prognostic ability of risk score.
A total of 8 mRNAs which were significantly related to the survival and prognosis of MM patients were obtained (<0.01). As molecular markers, MM patients could be divided into high-risk group and low-risk group. Survival curve and risk curve showed that the overall survival time of patients in the low-risk group was significantly better than that in the high risk group (<0.001). GSEA results showed that signal pathways related to basic metabolism, cell differentiation and cell cycle were significantly enriched in the high-risk group, while ribosome and N polysaccharide biosynthesis signaling pathway were more enriched in the low-risk group. Multivariate Cox regression analysis showed that the risk score composed of the eight metabolism-related genes could be used as an independent risk factor for the prognosis of MM patients, and receiver operating characteristic curve (ROC) showed that the molecular signatures of metabolism-related genes had the best predictive effect.
Metabolism-related pathways play an important role in the pathogenesis and prognosis of patients with MM. The clinical significance of the risk assessment model for patients with MM constructed based on eight metabolism-related core genes needs to be confirmed by further clinical studies.
筛选多发性骨髓瘤(MM)患者代谢基因的预后生物标志物,并构建代谢基因预后模型。
检索与MM患者相关的组织学数据库。选择具有完整临床信息的MM患者和健康对照的数据进行分析。从人类蛋白质图谱(HPA)和多发性骨髓瘤研究基金会(MMRF)数据库收集MM患者和健康对照骨髓组织的二代测序数据及临床信息。通过Perl语言从分子特征数据库(MSigDB)中提取代谢相关通路的基因集。通过差异分析、单因素Cox风险回归分析和LASSO回归分析筛选与MM代谢相关的生物标志物,并构建风险预后模型和列线图。采用风险曲线和生存曲线验证模型的分组效果。运用基因集富集分析(GSEA)研究高风险组和低风险组生物通路富集差异。采用多因素Cox风险回归分析验证风险评分的独立预后能力。
共获得8个与MM患者生存和预后显著相关的mRNA(<0.01)。作为分子标志物,MM患者可分为高风险组和低风险组。生存曲线和风险曲线显示,低风险组患者的总生存时间明显优于高风险组(<0.001)。GSEA结果显示,与基础代谢、细胞分化和细胞周期相关的信号通路在高风险组显著富集,而核糖体和N聚糖生物合成信号通路在低风险组更富集。多因素Cox回归分析显示,由8个代谢相关基因组成的风险评分可作为MM患者预后的独立危险因素,受试者工作特征曲线(ROC)显示,代谢相关基因的分子特征具有最佳预测效果。
代谢相关通路在MM患者的发病机制和预后中起重要作用。基于8个代谢相关核心基因构建的MM患者风险评估模型的临床意义有待进一步临床研究证实。