An efficient five-lncRNA signature for lung adenocarcinoma prognosis, with AL606489.1 showing sexual dimorphism

Background: Lung adenocarcinoma (LUAD) is a sex-biased and easily metastatic malignant disease. A signature based on 5 long non-coding RNAs (lncRNAs) has been established to promote the overall survival (OS) prediction effect on LUAD. Methods: The RNA expression profiles of LUAD patients were obtained from The Cancer Genome Atlas. OS-associated lncRNAs were identified based on the differential expression analysis between LUAD and normal samples followed by survival analysis, univariate and multivariate Cox proportional hazards regression analyses. OS-associated lncRNA with sex dimorphism was determined based on the analysis of expression between males and females. Functional enrichment analysis of the Gene Ontology (GO) terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was performed to explore the possible mechanisms of 5-lncRNA signatures. Results: A 5-lncRNA signature (composed of AC068228.1, SATB2-AS1, LINC01843, AC026355.1, and AL606489.1) was found to be effective in predicting high-risk LUAD patients as well as applicable to female and male subgroups and <65-year and ≥65-year age subgroups. The forecasted effect of the 5-lncRNA signature was more efficient and stable than the TNM stage and other clinical risk factors (such as sex and age). Functional enrichment analysis revealed that the mRNA co-expressed with these five OS-related lncRNAs was associated with RNA regulation within the nucleus. AL606489.1 demonstrated a sexual dimorphism that may be associated with microtubule activity. Conclusion: Our 5-lncRNA signature could efficaciously predict the OS of LUAD patients. AL606489.1 demonstrated gender dimorphism, which provides a new direction for mechanistic studies on sexual dimorphism.