Comprehensive proteomic and pathological profiling identifies PRAS40 as a novel biomarker and mediator of primary immune checkpoint blockade resistance in non-small cell lung cancer.

ABSTRACT:

Background

Immune checkpoint blockade (ICB) has revolutionized the treatment landscape of non-small cell lung cancer (NSCLC), yet primary resistance remains a significant clinical challenge. Recent evidence implicates PRAS40 (AKT1S1) in regulating cellular survival and immune responses, but its role in immunotherapy resistance is not fully understood.

Methods

Transcriptomic data from TCGA and GTEx cohorts were analyzed to assess PRAS40 expression. Prognostic value was evaluated using Cox regression. Immune microenvironment features were characterized with CIBERSORT and TIMER. Predictive efficacy for ICB response was examined using TIDE and IPS. Plasma PRAS40 levels in 66 NSCLC patients receiving ICB were quantified by proximity extension assay (PEA), and multiplex immunohist

SUBMITTER: Mao N 

PROVIDER: S-EPMC12514079 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature