Abstract
BackgroundIncreasing evidence has demonstrated that long non-coding RNAs (lncRNAs) play a crucial part in maintaining genomic instability. We therefore identified genome instability-related lncRNAs and constructed a prediction signature for early stage lung adenocarcinoma (LUAD) as well in order for classification of high-risk group of patients and improvement of individualized therapies.MethodsEarly stage LUAD RNA-seq and clinical data from The Cancer Genome Atlas (TCGA) were randomly divided into training set (n = 177) and testing set (n = 176). A total of 146 genomic instability-associated lncRNAs were identified based on somatic mutation profiles combining lncRNA expression profiles from TCGA by the “limma R” package. We performed Cox regression analysis to develop this predictive indicator. We validated the prognostic signature by an external independent LUAD cohort with microarray platform acquired from the Gene Expression Omnibus (GEO).ResultsA genome instability-related six-lncRNA-based gene signature (GILncSig) was established to divide subjects into high-risk and low-risk groups with different outcomes at statistically significant levels. According to the multivariate Cox regression and stratification analysis, the GILncSig was an independent predictive factor. Furthermore, the six-lncRNA signature achieved AUC values of 0.745, 0.659, and 0.708 in the training set, testing set, and TCGA set, respectively. When compared with other prognostic lncRNA signatures, the GILncSig also exhibited better prediction performance.ConclusionThe prognostic lncRNA signature is a potent tool for risk stratification of early stage LUAD patients. Our study also provided new insights for identifying genome instability-related cancer biomarkers.
Highlights
Non-small cell lung cancer (NSCLC) is a lethal cancer that causes over 1 million deaths a year (Torre et al, 2015; Yan et al, 2020; Zhu et al, 2021)
A heatmap of 20 upregulated long non-coding RNAs (lncRNAs) and 20 downregulated lncRNAs with the most significant differences is shown in Supplementary Figure 1
These two groups were distinguished by the expression of a total of 146 lncRNAs
Summary
Non-small cell lung cancer (NSCLC) is a lethal cancer that causes over 1 million deaths a year (Torre et al, 2015; Yan et al, 2020; Zhu et al, 2021). The rising incidence of lung adenocarcinoma (LUAD), a major type of NSCLC, has become such a concerning issue that tends to surpass lung squamous carcinoma (Tong et al, 2018). The lack of early predictive biomarkers hurdles early screening and partly contributes to the stunning mortality. As lung cancer screening is increasingly performed, more early stage LUAD patients are diagnosed. Exploring novel prognostic biomarkers should be paid much attention to in order to make risk stratification and to offer the optimal therapy for LUAD patients. Increasing evidence has demonstrated that long non-coding RNAs (lncRNAs) play a crucial part in maintaining genomic instability. We identified genome instability-related lncRNAs and constructed a prediction signature for early stage lung adenocarcinoma (LUAD) as well in order for classification of high-risk group of patients and improvement of individualized therapies
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