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

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

Volume: 31 Issue: 34

Author(s): Yuxi Wei, Wei Zhong, Yalan Bi, Xiaoyan Liu, Qing Zhou, Jia Liu, Mengzhao Wang, Hong Zhang*Minjiang Chen*

Affiliation:

• Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100000, China

• Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100000, China

Abstract:

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

Aim: 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.

Methods: 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.

Result: 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.

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

Cite this article as:

Wei Yuxi, Zhong Wei, Bi Yalan, Liu Xiaoyan, Zhou Qing, Liu Jia, Wang Mengzhao, Zhang Hong*, Chen Minjiang*, Molecular Subtypes and Prognostic Models for Predicting Prognosis of Lung Adenocarcinoma based on MiRNA-related Genes, Current Medicinal Chemistry 2024; 31 (34) . https://dx.doi.org/10.2174/0929867331666230914151943