Integrative multiomic profiling of cfDNA methylation and EV-miRNAs identifies immunotherapy-outcome molecular subtypes in NSCLC.

ABSTRACT:

Background

Patients with non-small cell lung cancer (NSCLC) exhibit heterogeneous responses to immunotherapy (IT) with high resistance rates, highlighting the need for precise biomarkers of treatment outcomes.

Methods

In a prospective cohort study, we longitudinally assessed liquid biopsy samples from patients with NSCLC undergoing IT at four distinct time points (T1 pretreatment, T2 post-second cycle, T3 6 months, and T4 1 year). We profiled plasma-derived cell-free DNA methylation and extracellular vesicle-associated microRNAs from 79 patients with metastatic NSCLC treated with immune checkpoint inhibitors (ICIs). High-dimensional omics data were integrated using Multi-Omics Factor Analysis (MOFA2) to uncover latent molecular subtypes, which we termed MOFA-Derived Clusters

SUBMITTER: Onieva JL 

PROVIDER: S-EPMC12815181 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature