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与二硫化物化死亡相关的长链非编码RNA可准确预测子宫内膜癌的生存率和免疫治疗反应。

The disulfidptosis-related lncRNAs can predict survival and immunotherapy response accurately in endometrial carcinoma.

作者信息

Hong Lin, Fang Ya-Xing, Li Tao, He Yu-Feng, Jin Qin-Qin, Xu Xiao, Zhou Shu-Guang

机构信息

Department of Gynecology, Maternal and Child Health Center of Anhui Medical University, The Fifth Affiliated Clinical College of Anhui Medical University, Hefei, Anhui 230001, China.

Department of Women's Health Care, Maternal and Child Health Institute of Anhui Province, Anhui 230001, China.

出版信息

Cell Mol Biol (Noisy-le-grand). 2025 Apr 15;71(3):20-30. doi: 10.14715/cmb/2025.71.3.3.

Abstract

Endometrial cancer of the uterine corpus (ECUC) is a common malignancy among females. Disulfidptosis, a recently identified form of cellular death, is characterized by elevated SLC7A11 expression and limited glucose availability, making it a potential cancer treatment target. In this research, clinical data and transcriptome information from EC samples were accessed from the TCGA database. A disulfidptosis-related lncRNAs(DRLs) prognostic signature was developed by univariate/LASSO/multivariate regression analyses. Cellular pathways were identified through GO, KEGG, and GSEA analyses. Immune infiltration as well as tumor mutational burden (TMB) were evaluated. The TIDE algorithm and the GDSC database were utilized to predict how patients reacted to immunotherapy as well as anticancer drugs. Finally, the expressions of disulfidptosis-related lncRNAs were measured using RT-qPCR. Results: In this study, we identified 524 disulfidptosis-related lncRNAs and developed a prognostic signature consisting of five DRLs (AC022960.1, PRDX6-AS1, EMSLR, AL359715.3, AC103563.9). Our prognostic signature effectively stratified EC patients into high- and low-risk groups. Compared with the high-risk group, patients in the low-risk group exhibited better overall survival (OS). Additionally, ROC curves and concordance index (C-index) plots were used to assess the accuracy of our prognostic signature. The results demonstrated that the AUC values for 1-, 3-, and 5-year survival were 0.676, 0.712, and 0.722, respectively, indicating high predictive accuracy. Further analysis revealed significant differences between high- and low-risk groups in terms of TMB, drug sensitivity, and immune cell infiltration. PCR results showed that PRDX6-AS1, EMSLR, AL359715.3, and AC103563.9 were upregulated in EC cells, whereas AC022960.1 was downregulated. In conclusion, we developed a DRLs signature capable of predicting the TMB, prognosis, and immunological cell infiltration patterns, as well as the reactions to immunotherapy in EC patients.

摘要

子宫体子宫内膜癌(ECUC)是女性常见的恶性肿瘤。二硫化物诱导的细胞死亡是一种最近发现的细胞死亡形式,其特征是溶质载体家族7成员11(SLC7A11)表达升高且葡萄糖可用性受限,这使其成为潜在的癌症治疗靶点。在本研究中,从癌症基因组图谱(TCGA)数据库获取了子宫内膜癌样本的临床数据和转录组信息。通过单因素/套索/多因素回归分析建立了一种与二硫化物诱导的细胞死亡相关的长链非编码RNA(DRLs)预后特征。通过基因本体论(GO)、京都基因与基因组百科全书(KEGG)和基因集富集分析(GSEA)确定细胞通路。评估免疫浸润以及肿瘤突变负荷(TMB)。利用肿瘤免疫功能障碍和排斥(TIDE)算法以及癌症药物敏感性基因组学(GDSC)数据库预测患者对免疫治疗以及抗癌药物的反应。最后,使用逆转录定量聚合酶链反应(RT-qPCR)检测与二硫化物诱导的细胞死亡相关的长链非编码RNA的表达。结果:在本研究中,我们鉴定出524个与二硫化物诱导的细胞死亡相关的长链非编码RNA,并建立了一个由5个DRLs(AC022960.1、PRDX6反义RNA1(PRDX6-AS1)、EMSLR、AL359715.3、AC103563.9)组成的预后特征。我们的预后特征有效地将子宫内膜癌患者分为高风险组和低风险组。与高风险组相比,低风险组患者的总生存期(OS)更好。此外,受试者工作特征(ROC)曲线和一致性指数(C指数)图用于评估我们的预后特征的准确性。结果表明,1年、3年和5年生存率的曲线下面积(AUC)值分别为0.676、0.712和0.722,表明预测准确性高。进一步分析显示,高风险组和低风险组在TMB、药物敏感性和免疫细胞浸润方面存在显著差异。PCR结果显示,PRDX6-AS1、EMSLR、AL359715.3和AC103563.9在子宫内膜癌细胞中上调,而AC022960.1下调。总之,我们建立了一种DRLs特征,能够预测子宫内膜癌患者的TMB、预后和免疫细胞浸润模式以及对免疫治疗的反应。

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