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Background and Purpose <p>While protocadherins (PCDHs) are implicated in tumorigenesis, the clinical significance of the gamma-protocadherin cluster (PCDHG) in lung squamous cell carcinoma (LUSC) remains largely unexplored. This study aims to define the prognostic value of the PCDHG family in LUSC, with a particular focus on&#xa0;PCDHGA10, and to investigate its functional role.</p> Methods <p>We conducted a comprehensive pan-cancer analysis of PCDHGA10 using public databases (TCGA, GTEx, etc.) to evaluate its differential expression, prognostic significance, association with tumor immunity, genomic features, and drug sensitivity.&#xa0;Furthermore,&#xa0;the functional impact of PCDHGA10 on proliferation and invasion was experimentally validated in LUSC cell lines using Western blot, MTT, colony formation, and Transwell assays.</p> Results <p>Most PCDHG members were downregulated in LUSC and linked to patient prognosis.&#xa0;Notably,&#xa0;PCDHGA10 was identified as an independent prognostic factor. Our analysis also revealed that PCDHGA10 expression is associated with DNA methylation, tumor mutational burden, immune cell infiltration, and sensitivity to multiple therapeutic agents across various cancers.&#xa0;Critically,&#xa0;in vitro experiments confirmed that PCDHGA10 significantly suppresses the invasive capacity of LUSC cells.</p> Conclusion <p>Our study underscores the critical role of the PCDHG family, particularly&#xa0;PCDHGA10, as a novel biomarker for prognosis and immunotherapy response in LUSC and pan-cancer.&#xa0;These insights pave the way for new immunotherapeutic strategies targeting PCDHGA10-related pathways.</p> Graphical Abstract <p></p>

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From Family Screening to Functional Validation: PCDHGA10 Identified as a Key Prognostic and Tumor Suppressor Factor in Lung Squamous Cell Carcinoma

  • 期刊论文

  • 发表日期：

    2026年3月3日

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  • Ruijiao Lu,
  • Senyu Wang,
  • Yangchun Feng

摘要

Background and Purpose

While protocadherins (PCDHs) are implicated in tumorigenesis, the clinical significance of the gamma-protocadherin cluster (PCDHG) in lung squamous cell carcinoma (LUSC) remains largely unexplored. This study aims to define the prognostic value of the PCDHG family in LUSC, with a particular focus on PCDHGA10, and to investigate its functional role.

Methods

We conducted a comprehensive pan-cancer analysis of PCDHGA10 using public databases (TCGA, GTEx, etc.) to evaluate its differential expression, prognostic significance, association with tumor immunity, genomic features, and drug sensitivity. Furthermore, the functional impact of PCDHGA10 on proliferation and invasion was experimentally validated in LUSC cell lines using Western blot, MTT, colony formation, and Transwell assays.

Results

Most PCDHG members were downregulated in LUSC and linked to patient prognosis. Notably, PCDHGA10 was identified as an independent prognostic factor. Our analysis also revealed that PCDHGA10 expression is associated with DNA methylation, tumor mutational burden, immune cell infiltration, and sensitivity to multiple therapeutic agents across various cancers. Critically, in vitro experiments confirmed that PCDHGA10 significantly suppresses the invasive capacity of LUSC cells.

Conclusion

Our study underscores the critical role of the PCDHG family, particularly PCDHGA10, as a novel biomarker for prognosis and immunotherapy response in LUSC and pan-cancer. These insights pave the way for new immunotherapeutic strategies targeting PCDHGA10-related pathways.

Graphical Abstract