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Mishra, D.* ; Agrawal, S.* ; Malik, D.* ; Pathak, E. ; Mishra, R.*

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

Clin. Transl. Oncol., DOI: 10.1007/s12094-026-04569-1 (2026)
Postprint DOI PMC
Open Access Green
PURPOSE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Cancer-associated Fibroblasts ; Eml4–alk Fusion ; Non-small Cell Lung Cancer ; Tumor Microenvironment ; Mirna–mrna Regulation; Mesenchymal Transition; Clinical-outcomes; Cervical-cancer; R-package; Expression; Gene; Proliferation; Let-7; Identification; Network
ISSN (print) / ISBN 1699-048X
e-ISSN 1699-3055
Journal Clinical & translational oncology
Publisher Springer
Publishing Place Gewerbestrasse 11, Cham, Ch-6330, Switzerland
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Obesity (IDO)
Grants Government of India