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副斑点相关基因模块的综合分析揭示了多种癌症中的预后特征和免疫相关性。

Comprehensive analysis of paraspeckle-associated gene modules unveils prognostic signatures and immunological relevance in multi-cancers.

作者信息

Fan Zhuoyang, Yin Bowen, Chen Xiaochen, Yang Guowei, Zhang Wei, Ye Xiaodan, Han Hong, Li Ming, Shu Minfeng, Liu Rong

机构信息

Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Shanghai Institute of Medical Imaging, Fudan University, Shanghai, 200032, China.

出版信息

Discov Oncol. 2024 Aug 12;15(1):345. doi: 10.1007/s12672-024-01188-6.

DOI:10.1007/s12672-024-01188-6
PMID:39133261
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11319543/
Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, characterized by high rates of angiogenesis and immune evasion. Paraspeckle genes, involved in gene regulation and RNA metabolism, have recently been linked to tumor progression. This study aims to elucidate the relationship between paraspeckle genes and HCC prognosis, focusing on SFPQ, DDX39B, and UBAP2.

METHODS

We analyzed HCC (LIHC) and prostate cancer (PRAD) samples from the TCGA database to explore the correlation between paraspeckle genes and angiogenesis. We conducted unsupervised clustering, risk scoring, and survival analysis to identify distinct patient groups and their clinical outcomes. Gene expression data were used to perform differential analysis and Gene Ontology (GO) enrichment.

RESULTS

Our analysis identified significant correlations between paraspeckle genes and angiogenesis across multiple cancer types. Elevated expression levels of SFPQ, DDX39B, and UBAP2 were associated with poor prognosis in HCC patients, and all of them has statistical significance. Unsupervised clustering of HCC samples based on paraspeckle gene expression revealed two distinct clusters, with high-risk patients exhibiting stronger immune suppression and tumor immune evasion. GO enrichment highlighted critical pathways related to angiogenesis and immune regulation. Additionally, a risk scoring model based on these genes effectively distinguished high-risk and low-risk patient groups, providing valuable prognostic insights.

CONCLUSION

This study demonstrates that SFPQ, DDX39B, and UBAP2 are significantly associated with poor prognosis in HCC, likely due to their roles in promoting angiogenesis and immune suppression. These findings highlight the potential of paraspeckle genes as prognostic biomarkers and therapeutic targets, offering new avenues for personalized treatment strategies in HCC. Further research into their functional mechanisms and clinical applicability is crucial for advancing HCC treatment and improving patient outcomes.

摘要

背景

肝细胞癌(HCC)是全球癌症相关死亡的主要原因,其特征是血管生成率高和免疫逃逸。参与基因调控和RNA代谢的旁斑基因最近与肿瘤进展有关。本研究旨在阐明旁斑基因与HCC预后之间的关系,重点关注SFPQ、DDX39B和UBAP2。

方法

我们分析了来自TCGA数据库的HCC(LIHC)和前列腺癌(PRAD)样本,以探讨旁斑基因与血管生成之间的相关性。我们进行了无监督聚类、风险评分和生存分析,以确定不同的患者群体及其临床结果。基因表达数据用于进行差异分析和基因本体(GO)富集。

结果

我们的分析确定了多种癌症类型中旁斑基因与血管生成之间的显著相关性。HCC患者中SFPQ、DDX39B和UBAP2的表达水平升高与预后不良相关,且均具有统计学意义。基于旁斑基因表达对HCC样本进行无监督聚类,发现了两个不同的聚类,高风险患者表现出更强的免疫抑制和肿瘤免疫逃逸。GO富集突出了与血管生成和免疫调节相关的关键途径。此外,基于这些基因的风险评分模型有效地将高风险和低风险患者群体区分开来,提供了有价值的预后见解。

结论

本研究表明,SFPQ、DDX39B和UBAP2与HCC的不良预后显著相关,可能是由于它们在促进血管生成和免疫抑制中的作用。这些发现突出了旁斑基因作为预后生物标志物和治疗靶点的潜力,为HCC的个性化治疗策略提供了新途径。进一步研究它们的功能机制和临床适用性对于推进HCC治疗和改善患者预后至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fc3/11319543/6bed554d79a3/12672_2024_1188_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fc3/11319543/54bcc6621c55/12672_2024_1188_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fc3/11319543/2221ec2b2d14/12672_2024_1188_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fc3/11319543/984e6925e52d/12672_2024_1188_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fc3/11319543/6bed554d79a3/12672_2024_1188_Fig8_HTML.jpg

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Sublethal heat treatment enhances lactic acid uptake in macrophages via MCT1, leading to reduced paraspeckle formation and a subsequent decrease in macrophage pyroptosis.
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Hepatocellular Carcinoma: Latest Research in Pathogenesis, Detection and Treatment.肝细胞癌:发病机制、检测和治疗的最新研究。
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