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全面分析 POLH-AS1 作为肝细胞癌的预后生物标志物。

Comprehensive analysis of POLH-AS1 as a prognostic biomarker in hepatocellular carcinoma.

机构信息

Department of Hepatobiliary Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Department of Gynecological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.

出版信息

BMC Cancer. 2024 Sep 6;24(1):1112. doi: 10.1186/s12885-024-12857-8.

DOI:10.1186/s12885-024-12857-8
PMID:39242532
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11378586/
Abstract

BACKGROUND

Hepatocellular carcinoma (HCC), a prevalent primary malignant tumor, is notorious for its high mortality rate. Despite advancements in HCC treatment, patient outcomes remain suboptimal. This study endeavors to assess the potential prognostic significance of POLH-AS1 in HCC.

METHODS

In this research, we gathered RNA-Seq information from individuals with HCC in The Cancer Genome Atlas (TCGA). We analyzed the levels of POLH-AS1 expression in both HCC cells and tissues using statistical tests. Additionally, we examined various prognostic factors in HCC using advanced methodologies. Furthermore, we employed Spearman's rank correlation analysis to examine the association between POLH-AS1 expression and the tumor's immune microenvironment. Finally, the functional roles of POLH-AS1 in HCC were validated in two HCC cell lines (HEP3B and HEPG2).

RESULTS

Our analysis revealed elevated POLH-AS1 expression across various cancers, including HCC, with heightened expression correlating with HCC progression. Notably, POLH-AS1 expression emerged as a potential biomarker for HCC patient survival and prognosis. Mechanistically, we identified the involvement of POLH-AS1 in tumorigenesis pathways such as herpes simplex virus 1 infection, interactions with neuroactive receptors, and the cAMP signaling pathway. Lastly, inhibition of POLH-AS1 was discovered to hinder the proliferation, invasion and migration of HEP3B and HEPG2 HCC cells.

CONCLUSIONS

POLH-AS1 emerges as a promising prognostic biomarker and therapeutic target for HCC, offering potential avenues for enhanced patient management and treatment strategies.

摘要

背景

肝细胞癌(HCC)是一种常见的原发性恶性肿瘤,其死亡率很高。尽管 HCC 的治疗取得了进展,但患者的预后仍然不理想。本研究旨在评估 POLH-AS1 在 HCC 中的潜在预后意义。

方法

本研究从癌症基因组图谱(TCGA)中收集了 HCC 患者的 RNA-Seq 信息。我们使用统计检验分析了 HCC 细胞和组织中 POLH-AS1 的表达水平。此外,我们使用先进的方法学检查了 HCC 中的各种预后因素。此外,我们还使用 Spearman 秩相关分析检查了 POLH-AS1 表达与肿瘤免疫微环境之间的关联。最后,在两种 HCC 细胞系(HEP3B 和 HEPG2)中验证了 POLH-AS1 在 HCC 中的功能作用。

结果

我们的分析显示,POLH-AS1 在包括 HCC 在内的多种癌症中表达升高,表达水平升高与 HCC 进展相关。值得注意的是,POLH-AS1 表达可作为 HCC 患者生存和预后的潜在生物标志物。从机制上讲,我们发现 POLH-AS1 参与了肿瘤发生途径,如单纯疱疹病毒 1 感染、与神经活性受体的相互作用以及 cAMP 信号通路。最后,发现抑制 POLH-AS1 可阻碍 HEP3B 和 HEPG2 HCC 细胞的增殖、侵袭和迁移。

结论

POLH-AS1 作为 HCC 的有前途的预后生物标志物和治疗靶点,为改善患者管理和治疗策略提供了潜在途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eb5/11378586/e35f70000306/12885_2024_12857_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eb5/11378586/193f39bdab5c/12885_2024_12857_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eb5/11378586/e0c9ce987b98/12885_2024_12857_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eb5/11378586/53b9fff36262/12885_2024_12857_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eb5/11378586/afc673285e5c/12885_2024_12857_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eb5/11378586/e35f70000306/12885_2024_12857_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eb5/11378586/193f39bdab5c/12885_2024_12857_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eb5/11378586/08f408511e03/12885_2024_12857_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eb5/11378586/9bc4b6953220/12885_2024_12857_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eb5/11378586/e0c9ce987b98/12885_2024_12857_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eb5/11378586/53b9fff36262/12885_2024_12857_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eb5/11378586/afc673285e5c/12885_2024_12857_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eb5/11378586/e35f70000306/12885_2024_12857_Fig7_HTML.jpg

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