A novel prognostic model related to oxidative stress for treatment prediction in lung adenocarcinoma

Abstract

BackgroundThe prognostic model based on oxidative stress for lung adenocarcinoma (LUAD) remains unclear.MethodsThe information of LUAD patients were acquired from TCGA dataset. We also collected two external datasets from GEO for verification. Oxidative stress-related genes (ORGs) were extracted from Genecards. We performed machine learning algorithms, including Univariate Cox regression, Random Survival Forest, and Least Absolute Shrinkage and Selection Operator (Lasso) analyses on the ORGs to build the OS-score and OS-signature. We drew the Kaplan-Meier and time-dependent receiver operating characteristic curve (ROC) to evaluate the efficacy of the OS-signature in predicting the prognosis of LUAD. We used GISTIC 2.0 and maftool algorithms to explore Genomic mutation of OS-signature. To analyze characteristic of tumor infiltrating immune cells, ESTIMATE, TIMER2.0, MCPcounter and ssGSEA algorithms were applied, thus evaluating the immunotherapeutic strategies. Chemotherapeutics sensitivity analysis was based on pRRophetic package. Finally, PCR assays was also used to detect the expression values of related genes in the OS-signature in cell lines.ResultsTen ORGs with prognostic value and the OS-signature containing three prognostic ORGs were identified. The significantly better prognosis of LUAD patients was observed in LUAD patients. The efficiency and accuracy of OS-signature in predicting prognosis for LUAD patients was confirmed by survival ROC curves and two external validation data sets. It was clearly observed that patients with high OS-scores had lower immunomodulators levels (with a few exceptions), stromal score, immune score, ESTIMATE score and infiltrating immune cell populations. On the contrary, patients with higher OS-scores were more likely to have higher tumor purity. PCR assays showed that, MRPL44 and CYCS were significantly higher expressed in LUAD cell lines, while CAT was significantly lower expressed.ConclusionThe novel oxidative stress-related model we identified could be used for prognosis and treatment prediction in lung adenocarcinoma.

Investigating subtypes of lung adenocarcinoma by oxidative stress and immunotherapy related genes

“…Oxidative stress and immunotherapy have become focal points in LUAD research. Recently, a prognostic model related to oxidative stress was provided, with the AUC of 0.660 on the 5-year survival prediction 52 . Another research proposed a nomogram with a C-index of 0.684 (95% CI, 0.656–0.712) for the recurrence-free survival of LUAD, based on clinical and oxidative stress indicators 53 .…”

“…In previous research, the construction of prognostic models related to oxidative stress was often based on a limited number of datasets 52 , typically just two or three. This approach may have constrained the comprehensiveness and reliability of the findings.…”