ArticleBMC cancer2019
A subtype of oral, laryngeal, esophageal, and lung, squamous cell carcinoma with high levels of TrkB-T1 neurotrophin receptor mRNA.
Article in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- Clinical efficacy and identification of factors confer resistance to afatinib (tyrosine kinase inhibitor) in EGFR-overexpressing esophageal squamous cell carcinoma.Signal transduction and targeted therapy · 2024Trial
- Atlas-Guided Nanocarrier Strategies Targeting Spatial NTRK2/MAPK Signaling in EGFR-TKI-Resistant Niches of Esophageal Squamous Cell Carcinoma.Pharmaceutics · 2026Review
- Uveal Melanocytoma without GNAQ/GNA11 Mutations.Ocular oncology and pathology · 2025Article
- Serum BDNF helps identify favorable subgroups in HCC patients treated with PD-L1 inhibitors and anti-angiogenic TKIs.Therapeutic advances in medical oncology · 2025Article
- NTRK Gene Expression Analysis in Oral Squamous Cell Carcinoma Mexican Population.Dentistry journal · 2024Article
- Schwann Cells in Digestive System Disorders.Cells · 2022Review
- Clinical Value Screening, Prognostic Significance, and Key Gene Identification of TrkB in Laryngeal Carcinoma.Disease markers · 2022Article
- Comprehending the crosstalk between Notch, Wnt and Hedgehog signaling pathways in oral squamous cell carcinoma - clinical implications.Cellular oncology (Dordrecht, Netherlands) · 2021Review
- Exploiting unique features of the gut-brain interface to combat gastrointestinal cancer.The Journal of clinical investigation · 2021Review
- Genome-wide analysis identifies critical DNA methylations within NTRKs genes in colorectal cancer.Journal of translational medicine · 2021Article
- Full-Length TrkB Variant in NSCLC Is Associated with Brain Metastasis.BioMed research international · 2020Article
- The Down-Regulation of TrkB Alleviates the Malignant Biological Behavior and Cancer Stem-Like Property of Laryngeal Cancer.Cancer management and research · 2020Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe NTRK2 genetic locus encodes neurotrophin membrane receptors that play an important role in normal neural tissue plasticity, growth, and survival. One NTRK2-encoded protein is TrkB-FL, which can regulate multiple pathways relevant to cancer. A second NTRK2 gene mRNA isoform encodes TrkB-T1, a receptor that has a different cytoplasmic domain encoded in a mRNA with a unique 3' terminal exon.
methodTumors from The Cancer Genome Atlas (TCGA) and other studies were classified according to the expression of a single form of NTRK2 mRNA, TrkB-T1, identified by its unique 3' terminal exon. Analysis of differentially expressed genes in TrkB-T1 high expressers was done to determine if tumors enriched for TrkB-T1 mRNA were a uniform group independent of anatomic site.
resultsThe mRNA for TrkB-T1 is the most abundant NTRK2 gene mRNA in all squamous cell carcinomas (SCCs) in the TCGA database. Comparison of larynx SCC high TrkB-T1 RNA expressers to low expressers (n = 96) revealed gene expression differences consistent with the high TrkB-T1 tumors being more neural-like. The upregulated genes in the TrkB-T1 RNA high expressers also showed enrichment of pathways involved in retinol metabolism, hedgehog signaling, and the Nfe2l2 response, among other pathways. An examination of oral, esophagus, and lung SCCs (n = 284, 97, 501) showed induction of the same pathways among tumors that expressed high levels of TrkB-T1 mRNA. Proteins associated with regulation of the sonic hedgehog pathway, and the Nfe2l2 response, Tp63, and Keap1 and p62/SQSTM1 proteins, showed differential expression in larynx, oral and lung high TrkB1-T1 expresser SCCs. Unexpectantly, the relationship of high level TrkB-T1 expression to patient outcomes was SCC anatomic site specific. High TrkB-T1 mRNA levels in laryngeal SCC correlated with poor survival, but the opposite was true for lung SCC. This may be because pathways enriched in the TrkB high expressers, like those involving oncogenes NFE2L2, PIK3CA, and SOX2, are known to have SCC anatomic site-specific effects on progression.
conclusionsHigh level TrkB-T1 mRNA is a marker of a distinct SCC subtype enriched for at least 3 pathways relevant to tumor progression: Nfe2l2 response, retinol metabolism, and hedgehog signaling.
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