Development and Validation of a Prognostic Index Based on Genes Participating in Autophagy in Patients With Lung Adenocarcinoma

Abstract

BackgroundLung adenocarcinoma (LUAD) is a deadly respiratory system malignancy with poor prognosis. Autophagy is essential for the beginning, development, and therapy resistance of cancer. However, the expression of genes participating in autophagy in LUAD and their associations with prognosis remain unclear.MethodsPredictive genes participating in autophagy in LUAD samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were investigated. TCGA and GEO cohorts were divided into two risk groups, while the low-risk group having a longer overall survival (OS) time. This article aims to point out the interaction between genes participating in autophagy and immune function, immune checkpoints, and m6a in LUAD. The prediction model was designed for exploring least absolute shrinkage and selection operator (LASSO) regression. It has been revealed that gene expression and autophagy are inextricably connected.ResultsGenes participating in autophagy were shown to be somewhat overexpressed in the high-risk group even though no different clinical symptoms were present, indicating that they might be used in a model to predict LUAD prognosis. The majority of genes participating in autophagy prognostic signatures controlled immunological and tumor-related pathways, according to gene set enrichment analysis (GSEA). KRT6A, KYNU, IGFBP1, DKK1, PKP2, PLEK2, GAPDH, FLNC, and NTSR1 might be related to the oncology process for LUAD patients. CERS4, CMAHP, and PLEKHB1 have been identified as being associated with low risk in patients with LUAD. Furthermore, the immune function and m6a gene expression differed significantly between the two groups.ConclusionsGenes participating in autophagy are connected to the development and progression of LUAD. LUAD patients’ prognoses are often foreseen utilizing matched prognostic models. Genes participating in autophagy in LUAD may be therapeutic targets that ought to be investigated more.

Construction of a redox-related gene signature for overall survival prediction and immune infiltration in non-small-cell lung cancer

“…Additionally, a redox-related gene signature has been established in LUAD ( Xiao et al, 2022b ), which is only suitable for a subset of patients with NSCLC and also lacks reliable experimental verification. In the present study, the redox-related gene signature was first constructed in all the patients with NSCLC, and Kaplan–Meier survival curve showed that the high-risk group had a worse OS than the low-risk group, which was different from and cannot be replaced by the previously constructed signature using hypoxia-related gene ( Chen et al, 2022 ), pyroptosis-related gene ( Zhang and Yan, 2021 ; Li et al, 2022 ), autophagy-related gene ( Wu et al, 2021a ), and inflammatory response-related gene ( Zou et al, 2021 ) because it could be meaningful in exploring the value of the redox-related gene in initiation, progression, prognosis, and therapy of NSCLC. The previous prognostic signatures in other cancers showed better diagnostic performance, with an AUC value of more than 0.8 ( Qian et al, 2022 ; Zhang et al, 2022 ).…”

“…However, in the current study, the AUC value for OS at the 5 year periods was 0.657 in TCGA and 0.717 in GSE31210. Various researches showed that the AUC values of many signatures for lung cancer or NSCLC were more than 0.75 ( Wu et al, 2021a ; Li et al, 2021b ; Ouyang et al, 2021 ; Qu et al, 2021 ; Zhang and Yan, 2021 ; Zou et al, 2021 ; Wang et al, 2022b ; Chen et al, 2022 ; Li et al, 2022 ; Yang et al, 2022 ). Thus, the prognostic biomarkers or signatures with a higher AUC value need to be explored in the future.…”

“…Thus, the prognostic biomarkers or signatures with a higher AUC value need to be explored in the future. Moreover, the 12 genes in prognostic signature were validated using real-time PCR in NSCLC; thus its reliability is higher than the above-mentioned redox-related gene signature for clear cell renal cell carcinoma ( Wu et al, 2021b ), hepatocellular carcinoma ( Tu et al, 2021 ), LUAD ( Xiao et al, 2022b ), and hypoxia-related gene signature ( Chen et al, 2022 ), pyroptosis-related gene signature ( Zhang and Yan, 2021 ; Li et al, 2022 ), autophagy-related gene signature ( Wu et al, 2021a ), and inflammatory response-related signature ( Zou et al, 2021 ) for NSCLC. Moreover, the risk score positively correlated with the progression of NSCLC and was an independent prognostic factor for NSCLC adjusted for age and UICC stage.…”

“…However, the researchers have demonstrated that the construction of gene signature could predict better prognosis and therapy response. For instance, hypoxia-related gene signature ( Chen et al, 2022 ), pyroptosis-related gene signature ( Zhang and Yan, 2021 ; Li et al, 2022 ), autophagy-related gene signature ( Wu et al, 2021a ), and inflammatory response-related signature ( Zou et al, 2021 ) may better predict prognosis, influence immunological state and guide individualized therapy due to its multidimensional parameters.…”

A novel glutamine metabolism-related gene signature for prognostic prediction in patients with lung adenocarcinoma

“…We rstly revealed that AMDHD1 was highly expressed in LUAD and its overexpression was correlated with patients' poor outcome. GAPDH was found to be one of ve key genes related to prognosis and CD8 + T-cell in ltration in LUAD [22,23]. Moreover, Sakthidhasan et al [24] con rmed the apoptotic and anti-proliferative potential of GAPDH against human lung carcinoma.…”