Abstract
Lung adenocarcinoma (LUAD) is one of the most fatal malignant tumors harmful to human health. The complexity and behavior characteristics of long-non-coding RNA (lncRNA)-associated competing endogenous RNA (ceRNA) network in LUAD patients are still unclear. The purpose of this study was to elucidate the regulatory networks of dysregulated RNAs, view, and identify potential prognosis signatures involved in LUAD. The expression profiles of mRNAs, lncRNAs, and miRNAs were obtained from the TCGA database. In total, 2078 DEmRNAs, 257 DElncRNAs, and 101 DEmiRNAs were sorted out. A PPI network including 45 DEmRNAs was constructed. Ten hub genes in the PPI network associated with cell cycle-related pathways were identified and they played key roles in regulating cell proliferation. A total of three DEmiRNAs, seven DElncRNAs, and six DEmRNAs were enrolled in the ceRNA network. Except for certain genes without any published study reports, all the genes in the ceRNA network played an essential role in controlling tumor cell proliferation and were associated with prognosis in LUAD. Finally, based on step regression and Cox regression survival analysis, we identified four candidate biomarkers, including miR490, miR1293, LINC01740, and IGF2BP1, and established a risk model based on the four genes. Our study provided a global view and systematic dissection of the lncRNA-associated ceRNA network, and the identified four genes might be novel important prognostic factors involved in LUAD pathogenesis.
Highlights
IntroductionLung cancer remains the leading cause of cancer deaths. Lung cancer is usually recognized late in its natural history and have a poor prognosis, with an overall 5-year survival rate of 10–15% (Cagle et al, 2013)
Despite medical advances, lung cancer remains the leading cause of cancer deaths
Biological pathway annotation of DERNAs showed that the GPCR ligand binding process accumulated the largest number of dysregulated genes (86 DERNAs), which indicated that the pathway may play an important role in the development and progression of tumors
Summary
Lung cancer remains the leading cause of cancer deaths. Lung cancer is usually recognized late in its natural history and have a poor prognosis, with an overall 5-year survival rate of 10–15% (Cagle et al, 2013). Long-non-coding RNA (lncRNAs) are a class of RNA molecules with more than 200 nucleotides in length and have no evident open reading frames (Fatica and Bozzoni, 2014). These long molecules are dysregulated among cancers (Yan et al, 2015) and play key roles in gene regulation and carcinogenesis, including proliferation, survival, migration, and genomic stability (Gutschner et al, 2013; Castro-Oropeza et al, 2018). A previous study reported that CCNA2, CDC20, PBK, and TOP2A that interacted with CDK1 play vital roles in survival outcomes in human lung cancer. We concluded that these 10 hub genes play key roles in regulating cell proliferation in LUAD
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