EML4-ALK fusion rewires transcriptomic, miRNA, and CAF-associated programs in non-small cell lung cancer.

Authors

Divya Mishra, Shivangi Agrawal, Divya Malik, Ekta Pathak, Rajeev Mishra

Published in

Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. Oct 09, 2026. Epub Oct 09, 2026.

Abstract

This study presents an integrative analysis of paired mRNA/miRNA expression and tumor microenvironment features to characterize the molecular landscape associated with EML4-ALK fusion status in non-small cell lung cancer (NSCLC).
Using TCGA-derived fusion-positive and fusion-negative NSCLC cohorts, we compared three complementary layers of tumor biology: transcriptomic architecture, miRNA-mRNA regulatory networks, and immune-stromal composition.
Fusion-positive tumors exhibited a distinct molecular program characterized by metabolic and proteostasis reprogramming, including glycolytic and N-glycan biosynthetic pathways linked to endoplasmic reticulum protein processing and export. Relative to fusion-negative tumors, they also showed reduced stromal infiltration and attenuation of extracellular matrix, adhesion, calcium signaling, and cytokine-related transcriptional programs. Integrative miRNA analysis identified a fusion-associated, miR-3065-centered regulatory hub with predicted extracellular matrix- and adhesion-related targets,including PDGFRB, CTSK, COL4A2, SPARC, FBN1, and LUM, whereas fusion-negative tumorsshowed miRNA network alterations associated with proliferative and ciliary programs. Tumormicroenvironment analysis further distinguished the groups, with fusion-positive tumors showing reduced cancer-associated fibroblast infiltration.
These findings characterize distinct molecular and microenvironmental features associated with EML4-ALK fusion-positive NSCLC and identify candidate regulatory networks and biomarkers that, pendingvalidation, may inform subtype-specific therapeutic stratification.

PMID:
42853517
Bibliographic data and abstract were imported from PubMed on 10 Oct 2026.

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