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Purpose <p>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 <i>ETV1</i>-related single nucleotide polymorphisms (SNPs) in predicting prognosis remains unclear.</p> Methods <p>This study included 75 GIST patients. We focused on identifying tag SNPs in the <i>ETV1</i> 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 <i>ETV1</i> transcripts were investigated via the dual-luciferase reporter assay system.</p> Results <p>We found that the rs3735343 SNP, located in the 3’ untranslated region of <i>ETV1</i>, was significantly associated with progression-free survival (PFS) in GIST patients receiving imatinib (<i>P</i> = 0.008). Multivariate analysis identified tumor size (<i>P</i> = 0.032, Hazard Ratio [HR] = 4.173, 95% CI: 1.127–15.454) and rs3735343 (<i>P</i> = 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 (<i>P</i> = 0.04). Additionally, miR-4311 was found to specifically and negatively regulate <i>ETV1</i> mRNA levels associated with the rs3735343 risk allele in vitro.</p> Conclusion <p>This study reported <i>ETV1</i> 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.</p>

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

  • 期刊论文

  • 发表日期：

    2025年7月2日

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  • Wei Zhuang,
  • Minju Jo,
  • Haibo Qiu,
  • Wanlong Lin,
  • Min Huang,
  • Xueding Wang

摘要

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.