Oxidative stress could maintain different biological processes in human cancer. However, the effect of oxidative stress on lung adenocarcinoma (LUAD) should be studied. This study analyzed the expression and clinical importance of oxidative stress in LUAD in detail. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were employed for obtaining LUAD expression profiles. Based on oxidative stress-related genes, molecular subtypes substantially correlated with the LUAD prognosis were discovered with ConsensusClusterPlus. Differentially expressed genes (DEGs) among subtypes were found using the Limma software package. Least absolute shrinkage and selection operator- (Lasso-) Cox analysis was employed to create the polygenic risk model. RiskScore and clinically relevant features were used to create nomograms. By utilizing oxidative stress-related genes and reliable clustering, stable molecular subtypes were first discovered. The prognosis, clinical characteristics, route characteristics, and immunological characteristics of these three molecular subtypes were all different. Subsequently, by using differential expression genes among molecular subtypes and Lasso, 7 main genes linked with the oxidative stress phenotype were discovered. A prognostic risk model was also built on the basis of major genes associated with the oxidative stress phenotype. The model demonstrated a high level of resilience and was unaffected by clinical-pathological features. It played a stable predictive role in independent datasets. Ultimately, to improve the prognosis model and survival prediction, RiskScore (RS) was combined with clinicopathological variables, and a decision tree model was used. The model exhibited a high prediction accuracy as well as the ability to predict survival. This research found that oxidative stress-related genes have a major involvement in the onset and progression of LUAD and that they may influence LUAD susceptibility to immunotherapy and standard chemotherapy. Furthermore, the identified risk models for 7 genes linked with oxidative stress exhibited could assist clinical treatment decisions and prognosis prediction. The classifier could be used as a molecular diagnostic tool for assessing LUAD patients’ prognosis risk.
Lung cancer is still the major contributor to cancer-related mortality. Over 85% of patients suffer from non-small-cell lung cancer (NSCLC). Mucins (MUCs) are large glycoproteins secreted or membrane-bound produced by epithelial cells in normal and malignant tissues. They are the major components of the mucous gel that covers the surface of the respiratory epithelium. Certain MUCs have been used or proposed to act as biomarkers for lung cancer. Nevertheless, the expression, messenger ribonucleic acid (mRNA) levels, and the prognostic value of MUCs in NSCLC are yet to be investigated systematically. In this research, the biological information of MUC proteins in patients with NSCLC was examined using a series of databases. The results based on gene expression profiling interactive analysis (GEPIA) illustrated that the expression of MUC3A, MUC4, MUC5B, MUC13, MUC16, and MUC21 mRNAs was remarkably upmodulated in lung adenocarcinoma (LUAD) patients, whereas the MUC1 expression was downregulated in lung squamous cell carcinoma (LUSC) patients. Kaplan–Meier plotter (KM Plotter) analysis revealed that elevated mRNA expression levels of MUC3A and MUC16 were linked to unfavourable overall survival (OS) in NSCLC, while increased mRNA expression of MUC1 and MUC15 was linked to good OS, especially in LUAD patients. In addition, differential expression of MUC1, MUC3A/3B, MUC8, MUC12, MUC15, and MUC16 mRNA was linked to the prognoses of NSCLC patients with varied clinical-pathological subtypes. Genetic alterations of MUCs in NSCLC primarily involved mutations, fusion, amplification, deep deletion, and multiple alterations according to cancer genomics (cBioPortal). Therefore, we propose that combinations of MUC proteins can act as prognostic biomarkers and demonstrate the therapeutic potential for NSCLC-related therapy.
Lung adenocarcinoma (LUAD) is the most common subtype of nonsmall cell lung cancer. Cytochrome c (Cyt c), which is produced from mitochondria, interacts with a protein called Apaf-1 to form the heptameric apoptosome. This heptameric apoptosome then activates the caspase cascade, which ultimately results in the execution of apoptosis. The purpose of our research was to discover a new prognostic model that is based on cytochrome c-related genes (CCRGs) for LUAD patients. Through LASSO regression analysis conducted on the LUAD datasets included in the TCGA datasets, a CCRGs signature was created. The diagnostic accuracy of the multigene signature was verified by an independent source using the GSE31210 and GSE72094 datasets. The GO and KEGG enrichment analysis were performed. In this study, there were 159 differentially expressed CCRGs in the TCGA dataset, while there were 68 differentially expressed CCRGs in the GSE31210 dataset. Additionally, there were 57 genes that overlapped across the two datasets. Using LASSO and Cox regression analysis, a signature consisting of 12 differentially expressed CCRGs was developed from the total of 57 such genes. On the basis of their risk ratings, patients were categorized into high-risk and low-risk categories, with low-risk patients having lower risk scores and a greater likelihood of surviving the disease. Univariate and multivariate analyses both concluded that this signature is an independent risk factor for LUAD. ROC curves demonstrated that this risk signature is capable of accurately predicting the 1-year, 2-year, 3-year, and 5-year survival rates of patients who have LUAD. The infiltration of antigen-presenting cells was higher in the low-risk group, such as aDCs, DCs, pDCs, and iDCs. The expression of multiple immune checkpoints was significantly higher in the low-risk group, such as BTLA, CD28, and CD86. Finally, we showed that the signature can be used to predict the drug sensitivity of already available or under investigational drugs. Overall, patient classification and individualized therapy options may benefit from this study’s development of a powerful gene signature with high value for prognostic prediction in LUAD.
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