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Background <p>Pleuropulmonary blastoma (PPB) is a rare pediatric sarcoma often associated with <i>DICER1</i> mutations. However, additional genetic factors may influence disease progression and prognosis. This study identifies a novel mutation in the <i>GPC3</i> gene and evaluates its potential as a prognostic biomarker in PPB.</p> Methods <p>Whole-genome sequencing (WGS) was conducted on blood samples from a three-generation family with PPB. Candidate genes were prioritized based on autosomal recessive inheritance patterns and association with PPB. Immunohistochemistry was used to assess <i>GPC3</i> expression in PPB tumor tissues, adjacent areas, and congenital pulmonary airway malformation (CPAM) samples. Kaplan-Meier survival analysis was performed, comparing survival outcomes in patients with varying levels of <i>GPC3</i> expression.</p> Results <p>Seventeen candidate genes, including <i>GPC3</i>, were identified. A novel missense mutation in the <i>GPC3</i> gene was confirmed, with significantly higher <i>GPC3</i> expression observed in PPB tissues than in CPAM or adjacent non-tumor tissues. Survival analysis revealed that patients with high <i>GPC3</i> expression (<i>GPC3</i>+++) exhibited a markedly lower two-year survival rate (30%) compared to moderate (<i>GPC3</i>++, 75%) and low (<i>GPC3</i>+, 90.9%) expression groups (<i>p</i> = 0.0035). The correlation between elevated <i>GPC3</i> levels and poor prognosis suggests <i>GPC3</i> as a potential biomarker for disease severity in PPB.</p> Conclusion <p>Our findings propose <i>GPC3</i> as a novel mutation contributing to PPB susceptibility and progression. Elevated <i>GPC3</i> expression correlates with poorer survival outcomes, indicating its potential as a prognostic marker and therapeutic target in PPB management.</p>

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GPC3: a novel mutated gene in pleuropulmonary blastoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月16日

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  • Jiahang Zeng,
  • Xinying Wang,
  • Yingyi Xu,
  • Qinglin Yang,
  • Junzheng Peng,
  • Fenghua Wang,
  • Jue Tang,
  • Dongmei Huang,
  • Jiachi Liao,
  • Yunyu He,
  • Lin Huang,
  • Jianhua Liang,
  • Le Li,
  • Zefeng Lin

摘要

Background

Pleuropulmonary blastoma (PPB) is a rare pediatric sarcoma often associated with DICER1 mutations. However, additional genetic factors may influence disease progression and prognosis. This study identifies a novel mutation in the GPC3 gene and evaluates its potential as a prognostic biomarker in PPB.

Methods

Whole-genome sequencing (WGS) was conducted on blood samples from a three-generation family with PPB. Candidate genes were prioritized based on autosomal recessive inheritance patterns and association with PPB. Immunohistochemistry was used to assess GPC3 expression in PPB tumor tissues, adjacent areas, and congenital pulmonary airway malformation (CPAM) samples. Kaplan-Meier survival analysis was performed, comparing survival outcomes in patients with varying levels of GPC3 expression.

Results

Seventeen candidate genes, including GPC3, were identified. A novel missense mutation in the GPC3 gene was confirmed, with significantly higher GPC3 expression observed in PPB tissues than in CPAM or adjacent non-tumor tissues. Survival analysis revealed that patients with high GPC3 expression (GPC3+++) exhibited a markedly lower two-year survival rate (30%) compared to moderate (GPC3++, 75%) and low (GPC3+, 90.9%) expression groups (p = 0.0035). The correlation between elevated GPC3 levels and poor prognosis suggests GPC3 as a potential biomarker for disease severity in PPB.

Conclusion

Our findings propose GPC3 as a novel mutation contributing to PPB susceptibility and progression. Elevated GPC3 expression correlates with poorer survival outcomes, indicating its potential as a prognostic marker and therapeutic target in PPB management.