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铜死亡相关 lncRNAs 与肿瘤代谢和免疫微环境相关,并可预测胰腺癌患者的预后。

Cuproptosis-related lncRNAs are correlated with tumour metabolism and immune microenvironment and predict prognosis in pancreatic cancer patients.

机构信息

Department of Oncology, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Cancer Institute, Shanghai, China.

State Key Laboratory of Oncogenes and Related Genes, Department of Oncology, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

出版信息

IET Syst Biol. 2023 Aug;17(4):174-186. doi: 10.1049/syb2.12068. Epub 2023 Jun 21.

Abstract

Cuproptosis is a novel cell death pathway, and the regulatory mechanism in pancreatic cancer (PC) is unclear. The authors aimed to figure out whether cuproptosis-related lncRNAs (CRLs) could predict prognosis in PC and the underlying mechanism. First, the prognostic model based on seven CRLs screened by the least absolute shrinkage and selection operator Cox analysis was constructed. Following this, the risk score was calculated for pancreatic cancer patients and divided patients into high and low-risk groups. In our prognostic model, PC patients with higher risk scores had poorer outcomes. Based on several prognostic features, a predictive nomogram was established. Furthermore, the functional enrichment analysis of differentially expressed genes between risk groups was performed, indicating that endocrine and metabolic pathways were potential regulatory pathways between risk groups. TP53, KRAS, CDKN2A, and SMAD4 were dominant mutated genes in the high-risk group and tumour mutational burden was positively correlated with the risk score. Finally, the tumour immune landscape indicated patients in the high-risk group were more immunosuppressive than that in the low-risk group, with lower infiltration of CD8+ T cells and higher M2 macrophages. Above all, CRLs can be applied to predict PC prognosis, which is closely correlated with the tumour metabolism and immune microenvironment.

摘要

铜死亡是一种新的细胞死亡途径,其在胰腺癌(PC)中的调控机制尚不清楚。作者旨在探讨铜死亡相关长非编码 RNA(CRL)是否可以预测 PC 的预后及其潜在机制。首先,通过最小绝对收缩和选择算子 Cox 分析筛选出的基于七个 CRL 的预后模型。在此基础上,计算胰腺癌患者的风险评分,并将患者分为高风险组和低风险组。在我们的预后模型中,风险评分较高的 PC 患者预后较差。基于几种预后特征,建立了一个预测列线图。此外,对风险组之间差异表达基因进行了功能富集分析,表明内分泌和代谢途径是风险组之间的潜在调节途径。TP53、KRAS、CDKN2A 和 SMAD4 是高危组中主要的突变基因,肿瘤突变负担与风险评分呈正相关。最后,肿瘤免疫图谱表明高危组患者比低危组患者更具免疫抑制性,CD8+T 细胞浸润较低,M2 巨噬细胞浸润较高。综上所述,CRL 可用于预测 PC 的预后,与肿瘤代谢和免疫微环境密切相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af42/10439495/ce12e61a118e/SYB2-17-174-g003.jpg

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