The Tumor Stemness Indice mRNAsi can Act as Molecular Typing Tool for Lung Adenocarcinoma

Abstract

Due to the high heterogeneity, lung adenocarcinoma (LUAD) cannot be distinguished into precise molecular subtypes, thereby resulting in poor therapeutic effect and low 5-year survival rate clinically. Although the tumor stemness score (mRNAsi) has been shown to accurately characterize the similarity index of cancer stem cells (CSCs), whether mRNAsi can serve as an effective molecular typing tool for LUAD isn't reported to date. In this study, we first demonstrate that mRNAsi is significantly correlated with the prognosis and disease degree of LUAD patients, i.e., the higher the mRNAsi, the worse the prognosis and the higher the disease degree. Second, we identify 449 mRNAsi-related genes based on both weighted gene co-expression network analysis (WGCNA) and univariate regression analysis. Third, our results display that 449 mRNAsi-related genes can accurately distinguish the LUAD patients into two molecular subtypes: ms-H subtype (with high mRNAsi) and ms-L subtype (with low mRNAsi), particularly the ms-H subtype has a worse prognosis. Remarkably, significant differences in clinical characteristics, immune microenvironment, and somatic mutation exist between the two molecular subtypes, which might lead to the poorer prognosis of the ms-H subtype patients than that of the ms-L subtype ones. Finally, we establish a prognostic model containing 8 mRNAsi-related genes, which can effectively predict the survival rate of LUAD patients. Taken together, our work provides the first molecular subtype related to mRNAsi in LUAD, and reveals that these two molecular subtypes, the prognostic model and marker genes may have important clinical value for effectively monitoring and treating LUAD patients.

Keywords: Cancer stem cells; Lung adenocarcinoma; Molecular subtype; Prognosis; mRNAsi.