School of Life Science, Liaoning University, Shenyang, 110036, China.
School of Pharmaceutical Sciences, Liaoning University, Shenyang, 110036, China.
Sci Rep. 2023 May 31;13(1):8822. doi: 10.1038/s41598-023-35167-8.
Oxidative stress, as a characteristic of cellular aerobic metabolism, plays a crucial regulatory role in the development and metastasis of gastric cancer (GC). Long noncoding RNAs (lncRNAs) are important regulators in GC development. However, research on the prognostic patterns of oxidative stress-related lncRNAs (OSRLs) and their functions in the immune microenvironment is currently insufficient. We identified the OSRLs signature (DIP2A-IT1, DUXAP8, TP53TG1, SNHG5, AC091057.1, AL355001.1, ARRDC1-AS1, and COLCA1) from 185 oxidative stress-related genes in The Cancer Genome Atlas (TCGA) cohort via random survival forest and Cox analyses, and the results were subsequently validated in the Gene Expression Omnibus (GEO) dataset. The patients were divided into high- and low-risk groups by the risk score of the OSRLs signature. Longer overall survival was detected in the low-risk group than in the high-risk group in both the TCGA cohort (P < 0. 001, HR = 0.43, 95% CI 0.31-0.62) and the GEO cohort (P = 0.014, HR = 0.67, 95% CI 0.48-0.93). Next, multivariate Cox analysis identified that the risk model was an independent prognostic characteristic (HR > 1, P = 0.005), and time-dependent receiver operating characteristic (ROC) curve analysis and nomogram analysis were utilized to evaluate the predictive ability of the risk model. Next, gene set enrichment analysis revealed that the immune-related pathway, Wnt/[Formula: see text]-catenin signature, mammalian target of rapamycin complex 1 signature, and cytokine‒cytokine receptor interaction was enriched. High-risk patients were more responsive to CD200, TNFSF4, TNFSF9, and BTNL2 immune checkpoint blockade. The results of qRT‒PCR further proved the accuracy of our bioinformatic analysis. Overall, our study identified a novel OSRLs signature that can serve as a promising biomarker and prognostic indicator, which provides a personalized predictive approach for patient prognosis evaluation and treatment.
氧化应激作为细胞需氧代谢的一个特征，在胃癌（GC）的发展和转移中起着关键的调节作用。长链非编码 RNA（lncRNA）是 GC 发展中的重要调节因子。然而，目前对于氧化应激相关 lncRNA（OSRL）的预后模式及其在免疫微环境中的功能的研究还不够充分。我们通过随机生存森林和 Cox 分析从癌症基因组图谱（TCGA）队列中的 185 个氧化应激相关基因中确定了 OSRL 特征（DIP2A-IT1、DUXAP8、TP53TG1、SNHG5、AC091057.1、AL355001.1、ARRDC1-AS1 和 COLCA1），并在基因表达综合数据库（GEO）数据集进行了验证。通过 OSRL 特征的风险评分，患者被分为高风险和低风险组。在 TCGA 队列（P<0.001，HR=0.43，95%CI 0.31-0.62）和 GEO 队列（P=0.014，HR=0.67，95%CI 0.48-0.93）中，低风险组的总生存期均长于高风险组。接下来，多变量 Cox 分析确定风险模型是一个独立的预后特征（HR>1，P=0.005），并利用时间依赖性接收者操作特征（ROC）曲线分析和列线图分析来评估风险模型的预测能力。接下来，基因集富集分析表明，免疫相关途径、Wnt/β-catenin 信号、哺乳动物雷帕霉素复合物 1 信号和细胞因子-细胞因子受体相互作用被富集。高危患者对 CD200、TNFSF4、TNFSF9 和 BTNL2 免疫检查点阻断更敏感。qRT-PCR 的结果进一步证明了我们生物信息学分析的准确性。总的来说，我们的研究确定了一个新的 OSRL 特征，它可以作为一个有前途的生物标志物和预后指标，为患者的预后评估和治疗提供了一种个性化的预测方法。
