Department of Infection, Chongqing Red Cross Hospital, Chongqing, China.
The Fifth Department of Tuberculosis, Chongqing Public Health Medical Center, Chongqing, China.
J Immunol Res. 2022 Jul 26;2022:6084589. doi: 10.1155/2022/6084589. eCollection 2022.
Lung adenocarcinoma (LUAD) has been the major cause of tumor-associated mortality in recent years and exhibits a poor outcome. New data revealed that peroxisomes have a function in the regulation of the development and progression of several tumors. However, the prognostic values of peroxisome-related genes (PRGs) were rarely reported. Genomic sequence, mutation, and clinical data of 535 LUAD tissues were obtained from TCGA data sets. Within the TCGA cohort, a multigene signature was constructed with the assistance of the LASSO Cox regression model. Three GEO data sets, including GSE3141, GSE31210, and GSE72094, were obtained as validation cohorts. ROC assays, Kaplan-Meier methods, and multivariate assays were applied to examine the prognostic capacities of the novel signature. Gene Set Enrichment Analysis (GSEA) was performed to further understand the underlying molecular mechanisms. In this study, we identified 47 differentially expressed peroxisome-related genes (PRGs), including 25 increased and 22 decreased PRGs. A prognostic model of six PRGs was established. The univariate and multivariate Cox analyses both showed that the value of risk score was less than 0.05. In LUAD patients, the strong connection between the risk score and overall survival was further verified in three other GEO data sets. TMB and cancer stem cell infiltration were shown to be significantly higher in the high-risk group in comparison to the low-risk group. The TIDE score of the group with the low risk was considerably greater than that of the group with the high risk. Several drugs, targeting PRG-related genes, were available for the treatments of LUAD. Overall, we developed a novel peroxisome-related prognostic signature for LUAD patients. This signature could successfully indicate LUAD patients' chances of survival as well as their immune system's responsiveness to treatments. In addition, it has the potential to serve as immunotherapeutic targets for LUAD patients.
肺腺癌 (LUAD) 近年来一直是肿瘤相关死亡的主要原因，预后较差。新数据显示，过氧化物酶体在几种肿瘤的发生和发展中具有调节作用。然而，过氧化物酶体相关基因 (PRGs) 的预后价值很少有报道。从 TCGA 数据集中获得了 535 例 LUAD 组织的基因组序列、突变和临床数据。在 TCGA 队列中，使用 LASSO Cox 回归模型构建了多基因特征。获得了三个 GEO 数据集，包括 GSE3141、GSE31210 和 GSE72094，作为验证队列。应用 ROC 检测、Kaplan-Meier 方法和多变量分析来检测新特征的预后能力。进行基因集富集分析 (GSEA) 以进一步了解潜在的分子机制。在这项研究中，我们鉴定了 47 个差异表达的过氧化物酶体相关基因 (PRGs)，包括 25 个上调和 22 个下调的 PRGs。建立了一个由 6 个 PRG 组成的预后模型。单因素和多因素 Cox 分析均显示风险评分值小于 0.05。在 LUAD 患者中，在另外三个 GEO 数据集中进一步验证了风险评分与总生存期之间的强联系。与低风险组相比，高风险组的 TMB 和癌症干细胞浸润显著更高。低风险组的 TIDE 评分明显大于高风险组。有几种针对 PRG 相关基因的药物可用于 LUAD 的治疗。总之，我们为 LUAD 患者开发了一种新的过氧化物酶体相关预后特征。该特征可以成功地指示 LUAD 患者的生存机会以及他们的免疫系统对治疗的反应性。此外，它有可能成为 LUAD 患者的免疫治疗靶点。
