一个新的与二硫键相关的长链非编码 RNA 预后风险模型:预测食管鳞状细胞癌的预后、肿瘤微环境和药物敏感性。

A novel disulfidptosis-related LncRNA prognostic risk model: predicts the prognosis, tumor microenvironment and drug sensitivity in esophageal squamous cell carcinoma.

机构信息

Department of Thoracic Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China.

Jiangxi Hospital of China-Japan Friendship Hospital, National Regional Center for Respiratory Medicine Nanchang, Nanchang, Jiangxi, 330000, People's Republic of China.

出版信息

BMC Gastroenterol. 2024 Nov 27;24(1):437. doi: 10.1186/s12876-024-03530-2.

Abstract

BACKGROUND

Disulfidptosis is a newly discovered type of cell death that differs from apoptosis, necrosis, ferroptosis and other death modes and is closely related to the occurrence and progression of tumors. However, the predictive potential and biological characteristics of disulfidptosis-related lncRNAs (DRGs-lncRNAs) in esophageal squamous cell carcinoma (ESCC) are unclear.

METHODS

RNA transcriptome data, clinical information and mutation data for ESCC patients were obtained from The Cancer Genome Atlas (TCGA) database. Pearson correlation and Cox regression analyses were used to identify the DRGs-lncRNAs associated with overall survival (OS). LASSO regression analysis was used to construct the prognostic model. A nomogram was created to predict the prognosis of patients with ESCC. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were used to identify the signaling pathways associated with the model. TIMER, CIBERSORT, ESTIMATE and other methods were used to analyze immune infiltration, immune function, immune checkpoints and drug sensitivity. The tumor mutation burden (TMB) were assessed between different risk groups. Real-time polymerase chain reaction (RT‒PCR) was used to detect the expression of DRGs-lncRNAs in ESCC cell lines.

RESULTS

A total of 155 lncRNAs significantly associated with disulfidptosis were identified. Through univariate Cox regression analysis, LASSO regression analysis and multivariate Cox regression analysis, 9 lncRNAs with independent prognostic significance were selected, and a prognosis model was established. Survival analysis with the prognostic model revealed that there were obvious differences in survival between the high- and low-risk groups. Further analysis revealed that the immune microenvironment, immune infiltration, immune function, immune checkpoints, and drug sensitivity significantly differed between the high-risk and low-risk groups. Patients who exhibited both high risk and high tumor mutation burden (TMB) survived shorter, while those who fell into the low risk and low TMB categories survived longer. In addition, RT‒PCR analysis revealed differential expression of DRG lncRNAs between ESCC cell lines and esophageal epithelial cell lines.

CONCLUSIONS

We established a DRG-lncRNA prognostic model that can be used to predict the prognosis, tumor mutation burden, immune cell infiltration, and drug sensitivity of ECSS patients. The results of this study provide valuable insights into the understanding of ESCC and provide valuable assistance for the individualized treatment of ESCC patients.

摘要

背景

二硫键凋亡是一种新发现的细胞死亡方式,与细胞凋亡、坏死、铁死亡等死亡方式不同,与肿瘤的发生发展密切相关。然而,食管鳞状细胞癌(ESCC)中与二硫键凋亡相关的长链非编码 RNA(DRGs-lncRNAs)的预测潜力和生物学特征尚不清楚。

方法

从癌症基因组图谱(TCGA)数据库中获取 ESCC 患者的 RNA 转录组数据、临床信息和突变数据。采用 Pearson 相关性分析和 Cox 回归分析鉴定与总生存期(OS)相关的 DRGs-lncRNAs。采用 LASSO 回归分析构建预后模型。建立列线图预测 ESCC 患者的预后。采用基因本体论(GO)、京都基因与基因组百科全书(KEGG)和基因集富集分析(GSEA)鉴定与模型相关的信号通路。采用 TIMER、CIBERSORT、ESTIMATE 等方法分析免疫浸润、免疫功能、免疫检查点和药物敏感性。评估不同风险组之间的肿瘤突变负担(TMB)。采用实时聚合酶链反应(RT-PCR)检测 ESCC 细胞系中 DRGs-lncRNAs 的表达。

结果

共鉴定出 155 个与二硫键凋亡显著相关的 lncRNA。通过单因素 Cox 回归分析、LASSO 回归分析和多因素 Cox 回归分析,选择了 9 个具有独立预后意义的 lncRNA,建立了预后模型。利用预后模型进行生存分析,发现高低风险组之间的生存差异明显。进一步分析表明,高低风险组之间的免疫微环境、免疫浸润、免疫功能、免疫检查点和药物敏感性存在显著差异。同时,具有高风险和高肿瘤突变负担(TMB)的患者生存时间更短,而处于低风险和低 TMB 类别的患者生存时间更长。此外,RT-PCR 分析显示 ESCC 细胞系与食管上皮细胞系之间 DRG lncRNAs 的表达存在差异。

结论

本研究建立了一个可以预测 ESCC 患者预后、肿瘤突变负担、免疫细胞浸润和药物敏感性的 DRG-lncRNA 预后模型。本研究结果为理解 ESCC 提供了有价值的见解,并为 ESCC 患者的个体化治疗提供了有价值的帮助。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3173/11603746/98722b24e020/12876_2024_3530_Fig1_HTML.jpg

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