A Comprehensive Analysis of Exosome-Related Long Noncoding RNAs as Prognostic Biomarkers and Therapeutic Targets in Head and Neck Squamous Cell Carcinoma

IF 2.2 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL International Journal of Clinical Practice Pub Date : 2024-08-22 DOI:10.1155/2024/9326222
Tianyi Liu, Zhan Zhao, Huidong Chen, Fu Huang, Yang Jiang, Binbin Xiao, Yuqing Wang, Qingquan Hua
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Abstract

Background. Long noncoding RNAs (lncRNAs) often facilitate cellular communication via exosomes. However, their specific roles in head and neck squamous cell carcinoma (HNSCC) are not well understood. Methods. We extracted data on exosome-related lncRNAs from exoRBase and collected transcriptional profiles and clinical details for HNSCC from the TCGA database. Data preprocessing and analyses incorporated Tumor Mutation Burden and Microsatellite Instability from Researcher’s Home and drug sensitivity information from Genomics of Drug Sensitivity in Cancer database. We developed a prognostic model using Cox regression and LASSO regression analysis, with subsequent multivariate analysis to identify significant prognostic indicators. We also constructed a nomogram to evaluate the model’s clinical relevance, performed Gene Set Enrichment Analysis (GSEA), and analyzed the immune microenvironment and therapy sensitivity using CIBERSORT and TIDE algorithms. Supporting in vitro experiments and statistical analyses were conducted. Results. Our comprehensive investigation revealed 17 exosome-associated lncRNAs critical for patient survival in HNSCC. This enabled the development of a prognostic model that effectively stratifies patients into high-risk and low-risk categories. These lncRNAs correlate with patient demographics and clinical characteristics such as age, gender, and tumor stage. GSEA highlighted significant gene expression differences between the risk groups, particularly in pathways related to muscle formation, cellular transition, and immune response. The analysis of the immune microenvironment showed distinct immune cell infiltration patterns in high-risk patients, indicative of compromised immune defenses. In addition, we explored the expression of critical immune checkpoints and their impact on immunotherapy efficacy, demonstrating that risk scores may predict treatment responses. Notably, LINC01564 was overexpressed in HNSCC, associated with poorer prognosis, enhanced xenobiotic metabolism, and altered immune cell infiltration. Experimental validation confirmed LINC01564’s role in promoting tumor cell proliferation, invasion, and migration, highlighting its therapeutic potential. Conclusions. Our study highlights the importance of exosome-associated lncRNAs in HNSCC, identifying 17 critical lncRNAs as vital prognostic markers. The upregulation of LINC01564, associated with poor outcomes and increased tumor aggressiveness, underscores its potential as a therapeutic target.

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全面分析作为头颈部鳞状细胞癌预后生物标志物和治疗靶点的外泌体相关长非编码 RNAs
背景。长非编码 RNA(lncRNA)通常通过外泌体促进细胞间的交流。然而,它们在头颈部鳞状细胞癌(HNSCC)中的具体作用尚不十分清楚。研究方法我们从exoRBase中提取了外泌体相关lncRNAs的数据,并从TCGA数据库中收集了HNSCC的转录谱和临床细节。数据预处理和分析纳入了研究者之家(Researcher's Home)的肿瘤突变负担和微卫星不稳定性以及癌症药物敏感性基因组学数据库(Genomics of Drug Sensitivity in Cancer)的药物敏感性信息。我们利用 Cox 回归和 LASSO 回归分析建立了一个预后模型,并随后进行了多变量分析,以确定重要的预后指标。我们还构建了一个提名图来评估模型的临床相关性,进行了基因组富集分析(Gene Set Enrichment Analysis,GSEA),并使用 CIBERSORT 和 TIDE 算法分析了免疫微环境和治疗敏感性。还进行了辅助体外实验和统计分析。结果我们的综合研究发现了17个与外泌体相关的lncRNA,它们对HNSCC患者的生存至关重要。这使得我们能够建立一个预后模型,有效地将患者分为高危和低危两类。这些lncRNA与患者的人口统计学特征和临床特征(如年龄、性别和肿瘤分期)相关。GSEA突出显示了风险组之间的重大基因表达差异,尤其是在与肌肉形成、细胞转化和免疫反应相关的通路中。对免疫微环境的分析表明,高危患者的免疫细胞浸润模式截然不同,这表明他们的免疫防御功能受到了损害。此外,我们还探索了关键免疫检查点的表达及其对免疫疗法疗效的影响,证明风险评分可预测治疗反应。值得注意的是,LINC01564 在 HNSCC 中过表达,这与预后较差、异生物代谢增强和免疫细胞浸润改变有关。实验验证证实了 LINC01564 在促进肿瘤细胞增殖、侵袭和迁移方面的作用,凸显了其治疗潜力。结论。我们的研究强调了外泌体相关lncRNA在HNSCC中的重要性,确定了17个关键lncRNA作为重要的预后标志物。LINC01564的上调与不良预后和肿瘤侵袭性增加有关,这突显了其作为治疗靶点的潜力。
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CiteScore
5.30
自引率
0.00%
发文量
274
审稿时长
3-8 weeks
期刊介绍: IJCP is a general medical journal. IJCP gives special priority to work that has international appeal. IJCP publishes: Editorials. IJCP Editorials are commissioned. [Peer reviewed at the editor''s discretion] Perspectives. Most IJCP Perspectives are commissioned. Example. [Peer reviewed at the editor''s discretion] Study design and interpretation. Example. [Always peer reviewed] Original data from clinical investigations. In particular: Primary research papers from RCTs, observational studies, epidemiological studies; pre-specified sub-analyses; pooled analyses. [Always peer reviewed] Meta-analyses. [Always peer reviewed] Systematic reviews. From October 2009, special priority will be given to systematic reviews. [Always peer reviewed] Non-systematic/narrative reviews. From October 2009, reviews that are not systematic will be considered only if they include a discrete Methods section that must explicitly describe the authors'' approach. Special priority will, however, be given to systematic reviews. [Always peer reviewed] ''How to…'' papers. Example. [Always peer reviewed] Consensus statements. [Always peer reviewed] Short reports. [Always peer reviewed] Letters. [Peer reviewed at the editor''s discretion] International scope IJCP publishes work from investigators globally. Around 30% of IJCP articles list an author from the UK. Around 30% of IJCP articles list an author from the USA or Canada. Around 45% of IJCP articles list an author from a European country that is not the UK. Around 15% of articles published in IJCP list an author from a country in the Asia-Pacific region.
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