Liu Jinhui, Geng Rui, Ni Senmiao, Cai Lixin, Yang Sheng, Shao Fang, Bai Jianling
Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China.
Department of Biostatistics, School of Public Heath, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing 211166, P.R. China.
Mol Ther Nucleic Acids. 2022 Jan 25;27:1036-1055. doi: 10.1016/j.omtn.2022.01.018. eCollection 2022 Mar 8.
Uterine corpus endometrial carcinoma (UCEC) is a malignant disease globally, and there is no unified prognostic signature at present. In our study, two clusters were identified. Cluster 1 showed better prognosis and higher infiltration level, such as tumor microenvironment (TME), tumor mutation burden (TMB), and immune checkpoint genes expression. Gene set enrichment analysis (GSEA) indicated that some tumor-related pathways and immune-associated pathways were exposed. What is more, six pyroptosis-related long noncoding RNAs (lncRNAs) (PRLs) were applied to establish a prognostic signature through multiple Cox regression analysis. In both training and testing sets, patients with higher risk score had poorer survival than patients with low risk. The area under the curve (AUC) of receiver operating characteristic (ROC) curves performed that the survival probability was better in people with lower risk score. Mechanism analysis revealed that high risk score was correlated with reduced immune infiltration and T cells exhaustion, matching the definition of an "immune-desert" phenotype. Patients with lower risk score were characterized by higher immune checkpoint gene expression and TMB and have a sensitive response to immunotherapy and chemotherapy compared with patients with high risk score. The signature has accurate prediction ability of UCEC and is a promising therapeutic target to improve the effect of immunotherapy.
子宫内膜癌(UCEC)是一种全球性的恶性疾病,目前尚无统一的预后特征。在我们的研究中,识别出了两个亚群。亚群1显示出更好的预后和更高的浸润水平,如肿瘤微环境(TME)、肿瘤突变负荷(TMB)和免疫检查点基因表达。基因集富集分析(GSEA)表明,一些肿瘤相关途径和免疫相关途径被揭示。此外,通过多因素Cox回归分析应用6个焦亡相关长链非编码RNA(lncRNA)(PRL)建立了一个预后特征。在训练集和测试集中,高风险评分的患者生存率均低于低风险患者。受试者工作特征(ROC)曲线的曲线下面积(AUC)表明,低风险评分人群的生存概率更高。机制分析显示,高风险评分与免疫浸润减少和T细胞耗竭相关,符合“免疫沙漠”表型的定义。与高风险评分患者相比,低风险评分患者的特征是免疫检查点基因表达和TMB更高,并且对免疫治疗和化疗反应敏感。该特征对UCEC具有准确的预测能力,是改善免疫治疗效果的一个有前景的治疗靶点。