High expression of the LAMA3/AC245041.2 gene pair associated with KRAS mutation and poor survival in pancreatic adenocarcinoma: A comprehensive TCGA analysis

Abstract

\n Background\n\nPancreatic adenocarcinoma (PAAD) is one of the worst cancers with high morbidity and mortality. Given that KRAS mutations may be an early event in PAAD. The present study aimed to identify differentially expression lncRNAs (DE-lncRNAs) and differentially expression mRNAs (DE-mRNAs) in KRAS-mutant PAAD. To explore the pathogenesis and molecular mechanism of PAAD development.\nMethods\n\nClinical data of TCGA-PAAD patients were downloaded from the TCGA database and survival analysis was carried out in combination with KRAS mutation information. Through weighted gene correlation network analysis (WGCNA) and univariate cox regression analysis, we constructed the prognostic risk models to identify the hub DEmRNAs and DElncRNAs associated with PAAD prognosis. GO and KEGG enrichment analysis of DE-mRNA was performed. Multivariate cox regression was used to analyze the overall prognosis of age, gender, pathologic_T and KRAS mutations, and then the differences in clinical characteristics of risk score1 and risk score2 were analyzed. Finally, the mRNAs-lncRNA-TFs regulatory network was constructed.\nResults\n\nThe functional enrichment analysis was performed after screening 1671 DE-mRNAs and 324 DE-lncRNA. It was found that the related pathways were mainly focused on the modulation of chemical synaptic transmission, synaptic membrane, ion-gated channel activity, ligand\u2009−\u2009receptor interactions that stimulate neural tissue, and so on. Univariate Cox regression analysis was used to screen 117 mRNAs and 36 lncRNAs, and the risk ratio models of mRNAs and lncRNAs was constructed. The LAMA3 (mRNA) and the AC245041.2 (lncRNA) have strong expression correlation in two risk models. The genes in the samples with high expression of the two genes were enriched into many transcription factors (TFs) related pathways, among which transcription factors related pathways including ATF5, CSHL1, NR1I2, SIPA1, HOXC13, HSF2, and HOXA10 were shared by the two groups, the core enrichment genes in the common TFs pathway were collated, and the regulatory network of mRNAs-lncRNAs-TFs was drawn.\nConclusion\n\nIn our study, new prognostic mRNAs and lncRNAs were identified, prognostic models were constructed respectively, and nomograms were constructed to guide clinical practice. We had drawn the regulatory network of mRNAs-lncRNAs-TFs, which can provide clues for further research in the future.