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基于焦亡相关 lncRNAs 的胃癌预后风险模型。

Prognosis Risk Model Based on Pyroptosis-Related lncRNAs for Gastric Cancer.

机构信息

Molecular Medicine and Cancer Research Center, Basic Medical College, Chongqing Medical University, Chongqing 400016, China.

出版信息

Biomolecules. 2023 Mar 3;13(3):469. doi: 10.3390/biom13030469.

Abstract

Gastric cancer (GC) is a malignant tumor with a low survival rate, high recurrence rate, and poor prognosis. With respect to this, pyroptosis is a type of programmed cell death that can affect the occurrence and development of tumors. Indeed, long non-coding RNAs (lncRNAs) were broadly applied for the purposes of early diagnosis, treatment, and prognostic analysis in regard to cancer. Based on the association of these three purposes, we developed a novel prognosis risk model based on pyroptosis-related lncRNAs (PRlncRNAs) for GC. The PRlncRNAs were obtained via univariate and multivariate Cox regression in order to build the predictive signatures. The Kaplan-Meier and gene set enrichment analysis (GSEA) methods were used to evaluate the overall survival (OS) and functional differences between the high- and low-risk groups. Moreover, the correlation of the signatures with immune cell infiltration was determined through single-sample gene set enrichment analysis (ssGSEA). Finally, we analyzed this correlation with the treatment responses in the GC patients; then, we performed quantitative reverse transcription polymerase chain reactions (qRT-PCRs) in order to verify the risk model. The high-risk group received a worse performance in terms of prognosis and OS when compared to the low-risk group. With respect to this, the area under the receiver operating characteristic curve (ROC) was found to be 0.808. Through conducting the GSEA, it was found that the high-risk groups possessed a significant enrichment in terms of tumor-immunity pathways. Furthermore, the ssGSEA revealed that the predictive features possessed strong associations with immune cell infiltration in regard to GC. In addition, we highlighted that anti-immune checkpoint therapy, combined with conventional chemotherapy drugs, may be more suitable for high-risk patients. The expression levels of LINC01315, AP003392.1, AP000695.2, and HAGLR were significantly different between the GC cell lines and the normal cell lines. As such, the six PRlncRNAs could be regarded as important prognostic biomarkers for the purposes of subsequent diagnoses, treatments, prognostic predictions, and the mechanism research of GC.

摘要

胃癌(GC)是一种恶性肿瘤,其生存率低、复发率高、预后差。在这方面,细胞焦亡是一种可以影响肿瘤发生和发展的程序性细胞死亡方式。实际上,长链非编码 RNA(lncRNA)广泛应用于癌症的早期诊断、治疗和预后分析。基于这三个目的的关联,我们开发了一种基于细胞焦亡相关 lncRNA(PRlncRNA)的 GC 新的预后风险模型。通过单变量和多变量 Cox 回归获得 PRlncRNA,以构建预测特征。使用 Kaplan-Meier 和基因集富集分析(GSEA)方法评估高风险组和低风险组之间的总生存期(OS)和功能差异。此外,通过单样本基因集富集分析(ssGSEA)确定特征与免疫细胞浸润的相关性。最后,我们分析了 GC 患者治疗反应与这些特征的相关性,并进行了定量逆转录聚合酶链反应(qRT-PCR)以验证风险模型。与低风险组相比,高风险组在预后和 OS 方面表现更差。在这方面,发现接收器操作特征曲线(ROC)的曲线下面积为 0.808。通过进行 GSEA,发现高风险组在肿瘤免疫途径方面存在显著富集。此外,ssGSEA 表明预测特征与 GC 中免疫细胞浸润具有很强的相关性。此外,我们强调,抗免疫检查点治疗联合常规化疗药物可能更适合高危患者。LINC01315、AP003392.1、AP000695.2 和 HAGLR 在 GC 细胞系和正常细胞系之间的表达水平存在显著差异。因此,这 6 个 PRlncRNA 可以作为 GC 后续诊断、治疗、预后预测和机制研究的重要预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdb8/10046686/8073f529b360/biomolecules-13-00469-g001.jpg

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