A risk stratification and prognostic prediction model for lung adenocarcinoma based on aging-related lncRNA

Abstract

Abstract To create a risk model of aging-related long non-coding RNAs (arlncRNAs) and determine whether they might be useful as markers for risk stratification, prognosis prediction, and targeted therapy guidance for patients with lung adenocarcinoma (LUAD). Data on aging genes and lncRNAs from LUAD patients were obtained from Human Aging Genomic Resources 3 and The Cancer Genome Atlas, and differential co-expression analysis of established differentially expressed arlncRNAs (DEarlncRNAs) was performed. They were then paired with a matrix of 0 or 1 by cyclic single pairing. The risk coefficient for each sample of LUAD individuals was obtained, and a risk model was constructed by performing univariate regression, least absolute shrinkage and selection operator regression analysis, and univariate and multivariate Cox regression analysis. Areas under the curve were calculated for the 1-, 3-, and 5-year receiver operating characteristic curves to determine Akaike information criterion-based cutoffs to identify high- and low-risk groups. The survival rate, correlation of clinical characteristics, malignant-infiltrating immune-cell expression, ICI-related gene expression, and chemotherapeutic drug sensitivity were contrasted with the high- and low-risk groups. We found that 99 DEarlncRNAs were upregulated and 12 were downregulated. Twenty pairs of DEarlncRNA pairs were used to create a prognostic model. The 1-, 3-, and 5-year survival curve areas of LUAD individuals were 0.805, 0.793, and 0.855, respectively. The cutoff value to classify patients into two groups was 0.992. The mortality rate was higher in the high-risk group. We affirmed that the LUAD outcome-related independent predictor was the risk score (p < 0.001). Validation of tumor-infiltrating immune cells and ICI-related gene expression differed substantially between the groups. The high-risk group was highly sensitive to docetaxel, erlotinib, gefitinib, and paclitaxel. Risk models constructed from arlncRNAs can be used for risk stratification in patients with LUAD and serve as prognostic markers to identify patients who might benefit from targeted and chemotherapeutic agents.