Lou Yabo, Wang Honggang, Wang Qunzhi, Shi Xin
Department of Respiratory and Critical Care Medicine, Jinhua People's Hospital, Jinhua City 321000, Zhejiang, China.
Department of Respiratory and Critical Care Medicine, Lanxi Hospital of Traditional Chinese Medicine, Lanxi City, 321100, Zhejiang, China.
J Formos Med Assoc. 2025 Mar 12. doi: 10.1016/j.jfma.2025.03.008.
Lung adenocarcinoma (LUAD) represents the primary tissue subtype of lung cancer, characterized by a significant mortality rate and unfavorable prognosis. Long non-coding RNAs (lncRNAs) serve as critical functional units in the initiation and progression of tumors. Peroxisomes, now recognized as vital organelles in tumor immune metabolism, have garnered considerable attention in recent research. Some LncRNAs regulate peroxisome protein conformation through the mechanism of RNA molecular chaperones to maintain its normal function. This study aims to investigate the role of peroxisome-related lncRNA signatures in predicting clinical outcomes and immunotherapy efficacy, as well as their correlation with drug sensitivity.
The genomic and clinical information stemmed from the Cancer Genome Atlas (TCGA) database, while the peroxisome-related genes came from relevant studies. We developed prognostic features through co-expression analysis, Cox regression analysis, and LASSO analysis. Then we classified patients into high-risk and low-risk cohorts and performed extensive model validations to assess the prognostic significance of the signature. We used RT-qPCR to detect the expression of six peroxisome-associated lncRNAs in lung adenocarcinoma cells. Following this, we analyzed immune-related functions and tumor mutation burden (TMB). Lastly, we identified potential drugs and evaluated the drug sensitivity for LUAD.
We identified six peroxisome-related lncRNAs that serve as prognostic biomarkers. Our analysis revealed that high-risk patients exhibited decreased survival rates and increased mortality. Independent prognostic evaluations, receiver operating characteristic (ROC) curves, and bar charts demonstrated that these peroxisome-related lncRNAs can effectively predict patient outcomes. RT-qPCR results also indicated that these peroxisomes showed significant differences in mRNA expression in lung normal and lung adenocarcinoma cells. Moreover, in high-risk individuals, we observed reduced immune cell infiltration, inhibited immune functions, and an elevated tumor mutational burden (TMB). Consequently, high-risk patients faced a higher likelihood of immune evasion, resulting in diminished effectiveness of immunotherapy.
In conclusion, the six lncRNAs linked to peroxisomes can reliably forecast the prognosis of LUAD patients and may offer novel perspectives for clinical applications and immunotherapy.
肺腺癌（LUAD）是肺癌的主要组织亚型，具有较高的死亡率和不良预后。长链非编码RNA（lncRNAs）在肿瘤的发生和发展中起着关键的功能作用。过氧化物酶体目前被认为是肿瘤免疫代谢中的重要细胞器，在最近的研究中受到了广泛关注。一些lncRNAs通过RNA分子伴侣机制调节过氧化物酶体蛋白构象，以维持其正常功能。本研究旨在探讨过氧化物酶体相关lncRNA特征在预测临床结局和免疫治疗疗效中的作用，以及它们与药物敏感性的相关性。
基因组和临床信息来源于癌症基因组图谱（TCGA）数据库，而过氧化物酶体相关基因来自相关研究。我们通过共表达分析、Cox回归分析和LASSO分析开发了预后特征。然后，我们将患者分为高风险和低风险队列，并进行了广泛的模型验证，以评估该特征的预后意义。我们使用RT-qPCR检测肺腺癌细胞中六种过氧化物酶体相关lncRNAs的表达。在此之后，我们分析了免疫相关功能和肿瘤突变负荷（TMB）。最后，我们确定了潜在药物并评估了对LUAD的药物敏感性。
我们鉴定出六种过氧化物酶体相关lncRNAs作为预后生物标志物。我们的分析表明，高风险患者的生存率降低，死亡率增加。独立预后评估、受试者工作特征（ROC）曲线和柱状图表明，这些过氧化物酶体相关lncRNAs可以有效地预测患者的结局。RT-qPCR结果还表明，这些过氧化物酶体在肺正常细胞和肺腺癌细胞中的mRNA表达存在显著差异。此外，在高风险个体中，我们观察到免疫细胞浸润减少、免疫功能受到抑制以及肿瘤突变负荷（TMB）升高。因此，高风险患者面临更高的免疫逃逸可能性，导致免疫治疗效果降低。
总之，与过氧化物酶体相关的六种lncRNAs可以可靠地预测LUAD患者的预后，并可能为临床应用和免疫治疗提供新的视角。
