未折叠蛋白反应相关基因在肝细胞癌中的预后作用。

IF 1.9 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Current protein & peptide science Pub Date : 2023-01-01 DOI:10.2174/1389203724666230816090504
Shuqiao Zhang, Xinyu Li, Yilu Zheng, Hao Hu, Jiahui Liu, Shijun Zhang, Chunzhi Tang, Zhuomao Mo, Weihong Kuang
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引用次数: 0

摘要

目的:揭示未折叠蛋白反应(UPR)相关基因在肝细胞癌(HCC)中的预后作用。背景:肝细胞癌是一种遗传异质性肿瘤,其预后预测仍然是一个挑战。阐明普遍定期审议分子机制的研究迅速增加。然而,HCC进展中相关基因的UPR分子亚型特征尚待深入研究。目的:对HCC患者UPR相关基因的预后特征进行全面评估,可以加深我们对HCC进展的细胞过程的理解,并为精确治疗提供创新策略。方法:基于HCC中UPR相关基因的表达谱,我们探索了UPR相关的基因介导的分子亚型,并构建了一个可以准确预测HCC预后的UPR相关信号基因。结果:利用HCC患者的微阵列数据,在恶性肿瘤和正常组织中发现了差异表达的UPR相关性基因(DEGs)。基于对UPR的DEGs修饰,NMF算法将HCC分为两种分子亚型。此外,我们开发了一个与UPR相关的模型来预测HCC患者的预后。UPR相关模型的稳健性在外部验证中得到了证实。此外,我们还分析了不同风险群体的免疫反应。免疫功能分析显示,Treg、巨噬细胞、aDCs和MHC I类在高危HCC中显著上调。同时,低风险亚组的细胞溶解活性和I型和II型INF反应较高。结论:本研究确定了两种HCC的UPR分子亚型,并建立了一个十基因HCC预后标志模型(EXTL3、PPP2R5B、ZBTB17、CCT3、CCT4、CCT5、GRPEL2、HSP90AA1、PDRG1和STC2),该模型可以有力地预测HCC的进展。
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Prognostic Role of Unfolded Protein Response-Related Genes in Hepatocellular Carcinoma.

Aims: To reveal the prognostic role of unfolded protein response (UPR) -related genes in hepatocellular carcinoma (HCC).

Background: Hepatocellular carcinoma is a genetically heterogeneous tumor, and the prediction of its prognosis remains a challenge. Studies elucidating the molecular mechanisms of UPR have rapidly increased. However, the UPR molecular subtype characteristics of the related genes in HCC progression have yet to be thoroughly studied.

Objective: Conducting a comprehensive assessment of the prognostic signature of genes related to the UPR in patients with HCC can advance our understanding of the cellular processes contributing to the progression of HCC and offer innovative strategies in precise therapy.

Methods: Based on the gene expression profiles associated with UPR in HCC, we explored the molecular subtypes mediated by UPR-related genes and constructed a UPR-related genes signature that could precisely predict the prognosis for HCC.

Results: Using microarray data of HCC patients, differentially expressed UPR-related genes (DEGs) were discovered in malignancies and normal tissues. The HCC was classified into two molecular subtypes by the NMF algorithm based on DEGs modification of the UPR. Moreover, we developed a UPR-related model for predicting HCC patients' prognosis. The robustness of the UPR- related model was confirmed in external validation. Moreover, we analyzed immune responses in different risk groups. Analysis of immune functions revealed that Treg, Macrophages, aDCs, and MHC class-I were significantly up-regulated in high-risk HCC. At the same time, cytolytic activity and type I and II INF response were higher in a low-risk subgroup.

Conclusion: This study identified two UPR molecular subtypes of HCC and developed a ten-gene HCC prognostic signature model (EXTL3, PPP2R5B, ZBTB17, CCT3, CCT4, CCT5, GRPEL2, HSP90AA1, PDRG1, and STC2), which can robustly forecast the progression of HCC.

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来源期刊
Current protein & peptide science
Current protein & peptide science 生物-生化与分子生物学
CiteScore
5.20
自引率
0.00%
发文量
73
审稿时长
6 months
期刊介绍: Current Protein & Peptide Science publishes full-length/mini review articles on specific aspects involving proteins, peptides, and interactions between the enzymes, the binding interactions of hormones and their receptors; the properties of transcription factors and other molecules that regulate gene expression; the reactions leading to the immune response; the process of signal transduction; the structure and function of proteins involved in the cytoskeleton and molecular motors; the properties of membrane channels and transporters; and the generation and storage of metabolic energy. In addition, reviews of experimental studies of protein folding and design are given special emphasis. Manuscripts submitted to Current Protein and Peptide Science should cover a field by discussing research from the leading laboratories in a field and should pose questions for future studies. Original papers, research articles and letter articles/short communications are not considered for publication in Current Protein & Peptide Science.
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