Department of Obstetrics and Gynecology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, Guangdong, PR China.
Key Laboratory of Research in Maternal and Child Medicine and Birth Defects, Guangdong Medical University, Foshan 528300, Guangdong, PR China.
Aging (Albany NY). 2021 Dec 1;13(23):25072-25088. doi: 10.18632/aging.203723.
Metabolic reprogramming is a common feature of tumor cells and is associated with tumorigenesis and progression. In this study, a metabolic gene-associated prognostic model (MGPM) was constructed using multiple bioinformatics analysis methods in cervical carcinoma (CC) tissues from The Cancer Genome Atlas (TCGA) database, which comprised fifteen differentially expressed metabolic genes (DEMGs). Patients were divided into a high-risk group with shorter overall survival (OS) and a low-risk group with better survival. Receiver operating characteristic (ROC) curve analysis showed that the MGPM precisely predicted the 1-, 3- and 5-year survival of CC patients. As expected, MGPM exhibited a favorable prognostic significance in the training and testing datasets of TCGA. And the clinicopathological parameters including stage, tumor (T) and metastasis (M) classifications had significant differences in low- and high-risk groups, which further demonstrated the MGPM had a favorite prognostic prediction ability. Additionally, patients with low-ESTMATEScore had a shorter OS and when those combined with high-risk scores presented a worse prognosis. Through "CIBERSORT" package and Wilcoxon rank-sum test, patients in the high-risk group with a poor prognosis showed lower levels of infiltration of T cell CD8 ( < 0.001), T cells memory activated ( = 0.010) and mast cells resting ( < 0.001), and higher levels of mast cells activated ( < 0.001), and we also found these patients had a worse response for immunosuppressive therapy. These findings demonstrate that MGPM accurately predicts survival outcomes in CC patients, which will be helpful for further optimizing immunotherapies for cancer by reprogramming its cell metabolism.
代谢重编程是肿瘤细胞的共同特征,与肿瘤发生和进展有关。在这项研究中,使用来自癌症基因组图谱(TCGA)数据库的宫颈癌细胞(CC)组织的多种生物信息学分析方法构建了代谢基因相关预后模型(MGPM),该模型包含十五个差异表达的代谢基因(DEMGs)。患者被分为总生存期(OS)较短的高风险组和生存状况较好的低风险组。接收者操作特征(ROC)曲线分析表明,MGPM 可准确预测 CC 患者的 1、3 和 5 年生存率。不出所料,MGPM 在 TCGA 的训练和测试数据集中表现出良好的预后意义。低风险组和高风险组的临床病理参数,包括分期、肿瘤(T)和转移(M)分类,存在显著差异,进一步证明了 MGPM 具有良好的预后预测能力。此外,ESTMATEScore 较低的患者 OS 更短,当与高风险评分结合时,预后更差。通过“CIBERSORT”包和 Wilcoxon 秩和检验,预后不良的高风险组患者中,T 细胞 CD8 浸润水平较低(<0.001),T 细胞记忆激活(=0.010)和静止肥大细胞(<0.001),而激活的肥大细胞(<0.001)水平较高,并且我们还发现这些患者对免疫抑制治疗的反应较差。这些发现表明,MGPM 可准确预测 CC 患者的生存结局,这将有助于通过重新编程其细胞代谢来进一步优化癌症的免疫疗法。