Distinct molecular subtypes of KRAS^G12C-mutant lung adenocarcinoma: Insights into clinical outcomes, tumour microenvironments and therapeutic strategies.

ABSTRACT:

Background

KRAS^G12C is the most common KRAS mutation in lung adenocarcinoma (LUAD), yet clinical responses to KRAS^G12C-selective inhibitors (G12Ci) and immunotherapy remain variable.

Methods

Transcriptomic analysis of KRAS^G12C-mutant LUAD was performed using machine learning algorithms to classify molecular subtypes. Subtype-specific features, including genomic alterations, tumour microenvironment and therapeutic vulnerabilities, were systematically evaluated.

Results

We identified three distinct molecular subtypes (KC1, KC2 and KC3) of KRAS^G12C-mutant LUAD through transcriptomic analysis using machine learning algorithms. KC1 subtype is characterised by a neuroendocrine phenotype associated with SMARCA4 loss-of-function and

SUBMITTER: Yang H 

PROVIDER: S-EPMC12481212 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature