Immune infiltration landscape on prognosis and therapeutic response and relevant epigenetic and transcriptomic mechanisms in lung adenocarcinoma

Abstract

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.

KLF4 as a Novel Prognostic Biomarker and Its Correlation with Immune Infiltrates in Lung Adenocarcinoma

“…In their study, Zhang and colleagues investigated ve lung adenocarcinoma (LUAD) datasets to analyze the immune in ltration landscape and identify relevant epigenetic and transcriptomic mechanisms. They discovered that seven immune cell types, including B cells, eosinophils, iDCs, mast cells, T cells, Tem, and Tfh cells, were signi cantly associated with LUAD prognosis and acted as risk factors [27]. Additionally, KLF4 was identi ed as a key regulator in M2 macrophage polarization, which is known to enhance immunity [28,29].…”

Abnormal low expression of SFTPC promotes the proliferation of lung adenocarcinoma by enhancing PI3K/AKT/mTOR signaling transduction

“…TME [ 31 ] is composed of immune and stromal cells. Immune infiltration plays an essential role in LUAD prognosis and therapeutic response [ 32 ]. Accumulating evidence suggests that immune checkpoint inhibitors (ICI) are extraordinarily beneficial for NSCLC patients.…”