Identification of a novel oxidative stress-related prognostic model in lung adenocarcinoma

Abstract

Background: Oxidative stress (OxS) participates in a variety of biological processes, and is considered to be related to the occurrence and progression of many tumors; however, the potential diagnostic value of OxS in lung cancer remains unclear.Methods: The clinicopathological and transcriptome data for lung adenocarcinoma (LUAD) were collected from TCGA and GEO database. LASSO regression was used to construct a prognostic risk model. The prognostic significance of the OxS-related genes was explored using a Kaplan-Meier plotter database. The prediction performance of the risk model was shown in both the TCGA and GSE68465 cohorts. The qRT-PCR was performed to explore the expression of genes. CCK-8, Edu and transwell assays were conducted to analyze the role of CAT on cell proliferation migration and invasion in lung cancer. Immune infiltration was evaluated by CIBERSORT and mutational landscape was displayed in the TCGA database. Moreover, the relationship between risk score with drug sensitivity was investigated by pRRophetic.Results: We identified a prognosis related risk model based on a four OxS gene signature in LUAD, including CYP2D6, FM O 3, CAT, and GAPDH. The survival analysis and ROC curve indicated good predictive power of the model in both the TCGA and GEO cohorts. LUAD patients in the high-risk group had a shorter OS compared to the low-risk group. QRT-PCR result showed that the expression of four genes was consistent with previous analysis in cell lines. Moreover, overexpression of CAT could decrease the proliferation, invasion and migration of lung cancer cells. The Cox regression analysis showed that the risk score could be used as an independent prognostic factor for OS. LUAD patients in the high-risk score group exhibited a higher tumor mutation burden and risk score were closely related to tumor associated immune cell infiltration, as well as the expression of immune checkpoint molecules. Both the high- and low-risk groups have significant differences in sensitivity to some common chemotherapy drugs, such as Paclitaxel, Docetaxel, and Vinblastine, which may contribute to clinical treatment decisions.Conclusion: We established a robust OxS-related prognostic model, which may contribute to individualized immunotherapeutic strategies in LUAD.

Identification of a novel oxidative stress-based molecular classification and treatment vulnerabilities in WHO grade II/III meningiomas

“…The threshold was set as |log2fold change| >0.585 and p < 0.05. The oxidative stressrelated gene set (Supplementary table 2) was gathered from prior literature [19,20]. Differentially expressed oxidative stress-related genes were subsequently acquired.…”

Redox Signaling Modulates Activity of Immune Checkpoint Inhibitors in Cancer Patients

“…To study the effect of OS on the prognosis of patients with lung adenocarcinoma (LUAD), Zhu et al created a prognostic risk score model and tested its predictive power in the TCGA and GEO cohorts [203]. To further examine the probable processes in LUAD, they divided the patients into two groups and then carried out analyses of immune cell infiltration, mutational landscape, immunological checkpoints, and correlation of treatment response.…”

“…Tumour-associated immune cell infiltration and immune checkpoint molecule expression were substantially correlated with each other, and the tumour mutation burden was higher in LUAD patients with high-risk scores. Between the high-and low-risk groups, there are considerable differences in drug sensitivity, which may have an impact on clinical treatment decisions and provide new knowledge for future anti-tumour immunotherapy [203].…”

Expression Pattern and Molecular Mechanism of Oxidative Stress-Related Genes in Myocardial Ischemia–Reperfusion Injury

“…Oxidative stress (OS) is an imbalance between oxidation and antioxidation in the body. The OS process releases a large number of reactive oxygen species (ROS), including superoxide anion, hydroxyl radical, and hydrogen peroxide [ 8 ]. Excessive ROS induces oxidative damage to proteins, lipids, and DNA, generates a large number of oxidative intermediates, increases neutrophil infiltration and protease secretion, activates the regulatory cell death process, and ultimately leads to tissue damage [ 9 ].…”