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构建与二硫键失调相关的 lncRNA 标志物,用于预测结肠腺癌的预后和免疫逃逸。

Construction of disulfidptosis-related lncRNA signature for predicting the prognosis and immune escape in colon adenocarcinoma.

机构信息

Department of General Surgery, Nanjing Tongren Hospital, School of Medicine, Southeast University, Nanjing, 211102, China.

Department of Pediatrics, Affiliated Hospital of Nanjing University of Chinese Medicine, Taicang Hospital of Traditional Chinese Medicine, Taicang, 215400, China.

出版信息

BMC Gastroenterol. 2023 Nov 10;23(1):382. doi: 10.1186/s12876-023-03020-x.

Abstract

Colon adenocarcinoma (COAD) is one of the most frequent types of cancer worldwide. Disulfidptosis has been identified as a new mode of cell death recently. The goal of this study was to explore the possibility of a connection between disulfidptosis and COAD. RNA sequencing data from COAD patients were retrieved from the The Cancer Genome Atlas (TCGA) database for this investigation. R software and various methods were used to identify disulfidptosis-related lncRNAs (DRLs) in COAD, and a prognostic model was created based on 6 DRLs (AP003555.1, AL683813.1, SNHG7, ZEB1-AS1, AC074212.1, RPL37A-DT). The prognostic model demonstrated a good accuracy in predicting the prognosis of COAD patients, according to receiver operating characteristic (ROC) curve and Concordance index (C-index) analyses. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed significant differences in biological functions and signaling pathways involved in differential genes in risk subgroups, including protein - DNA complex subunit organization, Hippo signaling pathway, Wnt signaling pathway. TIDE analysis was done on risk groupings in this study, and it found that patients in the high-risk group had more immune escape potential and were less probable to react to immunotherapy. Real-time quantitative pcr (qRT-PCR) was used to identify the relatively high expression of 6 DRLs in colon cancer cell lines. In summary, 6 DRLs were identified as possible novel molecular therapy targets for COAD in this investigation. This prognostic model has the potential to be a novel tool for forecasting COAD prognosis in clinical practice, as well as providing new insights on the potential function and mechanism of disulfidptosis in the COAD process.

摘要

结直肠癌(COAD)是全球最常见的癌症类型之一。最近,细胞死亡的新模式——二硫键凋亡已被确定。本研究旨在探讨二硫键凋亡与 COAD 之间可能存在的联系。本研究从癌症基因组图谱(TCGA)数据库中检索 COAD 患者的 RNA 测序数据。使用 R 软件和各种方法鉴定 COAD 中二硫键凋亡相关 lncRNA(DRLs),并基于 6 个 DRLs(AP003555.1、AL683813.1、SNHG7、ZEB1-AS1、AC074212.1、RPL37A-DT)构建预后模型。根据接收者操作特征(ROC)曲线和一致性指数(C-index)分析,该预后模型在预测 COAD 患者预后方面具有良好的准确性。基因本体论(GO)富集分析和京都基因与基因组百科全书(KEGG)富集分析显示,风险亚组差异基因涉及的生物学功能和信号通路存在显著差异,包括蛋白-DNA 复合物亚基组织、Hippo 信号通路、Wnt 信号通路。本研究对风险分组进行了 TIDE 分析,发现高风险组的患者具有更多的免疫逃逸潜力,对免疫治疗的反应可能性较小。实时定量 PCR(qRT-PCR)用于鉴定 6 个 DRLs 在结肠癌细胞系中的相对高表达。总之,本研究鉴定出 6 个 DRLs 可能是 COAD 的新分子治疗靶点。该预后模型有可能成为预测 COAD 预后的一种新的临床工具,并为二硫键凋亡在 COAD 过程中的潜在功能和机制提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a517/10636996/ce4eb513a3a5/12876_2023_3020_Fig1_HTML.jpg

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