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基于转录组数据的免疫相关长链非编码RNA特征鉴定肝细胞癌基因预后生物标志物

Identification of biomarkers of hepatocellular carcinoma gene prognosis based on the immune-related lncRNA signature of transcriptome data.

作者信息

Ma Andi, Sun Yukai, Ogbodu Racheal O, Xiao Ling, Deng Haibin, Zhou Hui

机构信息

Hunan University of Medicine School of Public Health and Laboratory Medicine, Huaihua, 418000, China.

Max Delbruck Centrum fur Molekulare Medizin Experimental and Clinical Research Center (MDC), AG Translational Oncology of Solid Tumors, Robert-Rössle-Straße 10, 13125, Berlin, Germany.

出版信息

Funct Integr Genomics. 2023 Mar 28;23(2):104. doi: 10.1007/s10142-023-01019-x.

Abstract

BACKGROUND

Long non-coding RNAs (lncRNAs) are well established to have an important role in cancer. The goal of this research was to investigate the prognostic usefulness of putative immune-related lncRNAs in hepatocellular carcinoma (HCC).

METHODS

The developed lncRNA signature was validated using 343 HCC patients from The Cancer Genome Atlas (TCGA) and 81 samples from Gene Expression Omnibus (GEO). Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) analysis were used to analyze immune-related lncRNAs for HCC prognosis. Patients in the low-risk group survived substantially longer than those in the high-risk group (P < 0.05). The discovered signal might be a useful prognostic factor for predicting patient survival. Overall survival predicted some clinical net improvements, according to the nomogram. Numerous enrichment approaches (including gene set enrichment analysis) were utilized to investigate the underlying mechanisms.

RESULTS

Drug metabolism, mTOR, and p53 signaling pathways were associated with high-risk groups. When the expression of lncRNA PRRT3-AS1 was silenced in HepG2 cells, the proliferation, migration, and invasion abilities of HepG2 cells were decreased, and apoptosis was enhanced. In the supernatant from HepG2 cells with PRRT3-AS1 knockdown, the anti-inflammatory factors IL-10 and TGF-1 were induced, whereas the pro-inflammatory factors IL-1β, TNF-α, and IL-6 were reduced (P < 0.05). After PRRT3-AS1 knockdown, the protein expression of CD24, THY1, LYN, CD47, and TRAF2 in HepG2 cells was attenuated (P < 0.05).

CONCLUSION

The discovery of five immune-related lncRNA signatures has significant therapeutic significance for predicting patient prognosis and directing personalized treatment for patients with HCC, which requires additional prospective confirmation.

摘要

背景

长链非编码RNA(lncRNAs)在癌症中具有重要作用已得到充分证实。本研究的目的是探讨假定的免疫相关lncRNAs在肝细胞癌(HCC)中的预后价值。

方法

使用来自癌症基因组图谱(TCGA)的343例HCC患者和来自基因表达综合数据库(GEO)的81个样本对开发的lncRNA特征进行验证。采用Cox回归和最小绝对收缩和选择算子(LASSO)分析来分析免疫相关lncRNAs对HCC预后的影响。低风险组患者的生存期明显长于高风险组患者(P < 0.05)。发现的信号可能是预测患者生存的有用预后因素。根据列线图,总生存期预测了一些临床净改善。采用多种富集方法(包括基因集富集分析)来研究潜在机制。

结果

药物代谢、mTOR和p53信号通路与高风险组相关。当lncRNA PRRT3-AS1在HepG2细胞中的表达被沉默时,HepG2细胞的增殖、迁移和侵袭能力降低,凋亡增强。在PRRT3-AS1敲低的HepG2细胞的上清液中,抗炎因子IL-10和TGF-1被诱导,而促炎因子IL-1β、TNF-α和IL-6减少(P < 0.05)。PRRT3-AS1敲低后,HepG2细胞中CD24、THY1、LYN、CD47和TRAF2的蛋白表达减弱(P < 0.05)。

结论

发现的五个免疫相关lncRNA特征对预测HCC患者的预后和指导个性化治疗具有重要的治疗意义,这需要进一步的前瞻性证实。

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