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Cancer Chemotherapy and Pharmacology

ETV1 genetic polymorphisms as a candidate prognosis biomarker of Gastrointestinal stromal tumor

Published in:
Authors
Wei Zhuang
Minju Jo
Haibo Qiu
Wanlong Lin
Min Huang
Xueding Wang
Published in
Cancer Chemotherapy and Pharmacology | Issue 1/2025

Abstract

Purpose

While imatinib is effective for treating Gastrointestinal Stromal Tumors (GISTs), significant variability in patient outcomes exists, highlighting the need for reliable prognostic biomarkers. ETV1, a key transcription factor involved in GIST progression, is implicated in disease biology, but the role of ETV1-related single nucleotide polymorphisms (SNPs) in predicting prognosis remains unclear.

Methods

This study included 75 GIST patients. We focused on identifying tag SNPs in the ETV1 gene and examined their association with clinical outcomes. Patient characteristics, somatic mutations, and imatinib concentration were also analyzed in a multivariate model. ETV1 expression was assessed using immunohistochemistry, and miRNA interactions with ETV1 transcripts were investigated via the dual-luciferase reporter assay system.

Results

We found that the rs3735343 SNP, located in the 3’ untranslated region of ETV1, was significantly associated with progression-free survival (PFS) in GIST patients receiving imatinib (P = 0.008). Multivariate analysis identified tumor size (P = 0.032, Hazard Ratio [HR] = 4.173, 95% CI: 1.127–15.454) and rs3735343 (P = 0.009, HR = 8.995, 95% CI: 1.712–47.255) as independent predictors of PFS. The rs3735343 risk allele also correlated with elevated ETV1 expression in GIST tissue (P = 0.04). Additionally, miR-4311 was found to specifically and negatively regulate ETV1 mRNA levels associated with the rs3735343 risk allele in vitro.

Conclusion

This study reported ETV1 rs3735343 as a novel prognostic candidate biomarker for GISTs treated with Imatinib, providing a potential biomarker for risk assessment of GIST. Additionally, our findings suggest that rs3735343 may act as a miRNA-regulated SNP, with miR-4311 playing a key role in its regulation.
Title
ETV1 genetic polymorphisms as a candidate prognosis biomarker of Gastrointestinal stromal tumor
Authors
Wei Zhuang
Minju Jo
Haibo Qiu
Wanlong Lin
Min Huang
Xueding Wang
Publication date
01-12-2025
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 1/2025
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-025-04789-2
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