ObjectiveLung adenocarcinoma (LUAD) is the most prevalent lung cancer subtype, but its immune infiltration features are not comprehensively understood. To address the issue, the present study was initiated to describe the immune infiltrations across LUAD from cellular compositional, functional, and mechanism perspectives.MethodsWe adopted five LUAD datasets (GSE32863, GSE43458, GSE75037, TCGA-LUAD, and GSE72094). Differentially expressed genes between LUAD and controls were selected for co-expression network analysis. Risky immune cell types were determined for classifying LUAD patients as diverse subtypes, followed by a comparison of antitumor immunity and therapeutic response between subtypes. Then, LUAD- and subtype-related key module genes affected by DNA methylation were determined for quantifying a scoring scheme. EXO1 was chosen for functional analysis via in vitro assays.ResultsTwo immune cell infiltration-based subtypes (C1 and C2) were established across LUAD, with poorer prognostic outcomes and lower infiltration of immune cell types in C1. Additionally, C1 presented higher responses to immune checkpoint blockade and targeted agents (JNK inhibitor VIII, BI-D1870, RO-3306, etc.). The scoring system (comprising GAPDH, EXO1, FYN, CFTR, and KLF4) possessed higher accuracy in estimating patients’ prognostic outcomes. EXO1 upregulation contributed to the growth, migration, and invasion of LUAD cells. In addition, EXO1 facilitated PD-L1 and sPD-L1 expression in LUAD cells.ConclusionAltogether, our findings offer a comprehensive understanding of the immune infiltration landscape on prognosis and therapeutic response of LUAD as well as unveil potential epigenetic and transcriptomic mechanisms, which might assist personalized treatment.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.