Molecular Subtypes and Prognostic Models for Predicting Prognosis of Lung Adenocarcinoma based on MiRNA-related Genes

MicroRNAs (miRNAs) are crucial in cancer development and progression, and therapies targeting miRNAs demonstrate great therapeutic promise.

We sought to predict the prognosis and therapeutic response of lung adenocarcinoma (LUAD) by classifying molecular subtypes and constructing a prognostic model based on miRNA-related genes.

This study was based on miRNA-mRNA action pairs and ceRNA networks in the Cancer Genome Atlas (TCGA) database. Three molecular subtypes were determined based on 64 miRNA-associated target genes identified in the ceRNA network. The S3 subtype had the best prognosis, and the S2 subtype had the worst prognosis. The S2 subtype had a higher tumor mutational load (TMB) and a lower immune score. The S2 subtype was more suitable for immunotherapy and sensitive to chemotherapy. The least absolute shrinkage and selection operator (LASSO) algorithm was performed to determine eight miRNA-associated target genes for the construction of prognostic models.

High-risk patients had a poorer prognosis, lower immune score, and lower response to immunotherapy. Robustness was confirmed in the Gene-Expression Omnibus (GEO) database cohort (GSE31210, GSE50081, and GSE37745 datasets). Overall, our study deepened the understanding of the mechanism of miRNA-related target genes in LUAD and provided new ideas for classification.

Such miRNA-associated target gene characterization could be useful for prognostic prediction and contribute to therapeutic decision-making in LUAD.