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Background <p>Baculoviral inhibitor of apoptosis protein repeat-containing protein 5 (BIRC5), also known as survivin, belongs to the inhibitor of apoptosis proteins (IAP) family and serves as a key regulator of cellular survival and programmed cell death. Current research has demonstrated that BIRC5 exhibits high expression levels in many cancers. Furthermore, its overexpression significantly correlates with poor clinical outcomes and contributes to tumor progression and metastasis.</p> Methods <p>We utilized TCGAplot R package (v8.0.0), Sangerbox3.0, GEPIA2, cBioPortal, UALCAN, TISIDB, BioGRID, and single-cell RNA sequencing (scRNA-seq) data to decipher the close association of BIRC5 with tumor occurrence and development as well as its involvement in gene mutations, methylation patterns, immune infiltration levels, functional aspects, and prognosis outcomes. Additionally, the expression of BIRC5 was assessed through western blot analysis following siRNA transfection in Lung adenocarcinoma (LUAD) cell lines. CCK-8 and Colony Formation Assays quantified proliferative changes in H1299 and A549 cells following BIRC5 downregulation.</p> Results <p>Pan-cancer&#xa0;analysis has demonstrated that BIRC5 expression is frequently upregulated in various tumor types. The dysregulation of BIRC5 has been strongly linked to poor clinical prognosis across various cancers. Moreover, alterations in BIRC5 gene have been observed in different tumors. Compared with normal tissues, the BIRC5 promoter region shows abnormal methylation levels in most cancer tissues. Additionally, BIRC5 is implicated in immune infiltration and immune cell composition with the tumor microenvironment (TME), suggesting its potential role in shaping the immunological landscape of cancer. The study also elucidates the correlation between BIRC5 and immune checkpoint (ICP) expression. Furthermore, scRNA-seq findings underscore the pivotal role played by BIRC5 in regulating a wide range of biological behaviors such as cell cycle progression, DNA damage, DNA repair response, proliferation, and invasion within tumors. Experimental evidence further confirms that knockdown of BIRC5 effectively inhibits LUAD proliferation.</p> Conclusion <p>Our research systematically highlighted the profound association between BIRC5 expression and various clinical characteristics, survival, mutation patterns, and TME in many cancers. These analyses yield valuable perspectives on BIRC5’s function across different cancers.</p>

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Comprehensive analysis of BIRC5: from pan-cancer analysis to experimental validation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月8日

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  • Guoliang Liao,
  • Jiekun Qian,
  • Shijie Wei,
  • Xin Yan,
  • Qing Liu,
  • Qinzhao Huang,
  • Yuxing Lin,
  • Guobing Xu,
  • Bin Zheng,
  • Chun Chen,
  • Zhang Yang

摘要

Background

Baculoviral inhibitor of apoptosis protein repeat-containing protein 5 (BIRC5), also known as survivin, belongs to the inhibitor of apoptosis proteins (IAP) family and serves as a key regulator of cellular survival and programmed cell death. Current research has demonstrated that BIRC5 exhibits high expression levels in many cancers. Furthermore, its overexpression significantly correlates with poor clinical outcomes and contributes to tumor progression and metastasis.

Methods

We utilized TCGAplot R package (v8.0.0), Sangerbox3.0, GEPIA2, cBioPortal, UALCAN, TISIDB, BioGRID, and single-cell RNA sequencing (scRNA-seq) data to decipher the close association of BIRC5 with tumor occurrence and development as well as its involvement in gene mutations, methylation patterns, immune infiltration levels, functional aspects, and prognosis outcomes. Additionally, the expression of BIRC5 was assessed through western blot analysis following siRNA transfection in Lung adenocarcinoma (LUAD) cell lines. CCK-8 and Colony Formation Assays quantified proliferative changes in H1299 and A549 cells following BIRC5 downregulation.

Results

Pan-cancer analysis has demonstrated that BIRC5 expression is frequently upregulated in various tumor types. The dysregulation of BIRC5 has been strongly linked to poor clinical prognosis across various cancers. Moreover, alterations in BIRC5 gene have been observed in different tumors. Compared with normal tissues, the BIRC5 promoter region shows abnormal methylation levels in most cancer tissues. Additionally, BIRC5 is implicated in immune infiltration and immune cell composition with the tumor microenvironment (TME), suggesting its potential role in shaping the immunological landscape of cancer. The study also elucidates the correlation between BIRC5 and immune checkpoint (ICP) expression. Furthermore, scRNA-seq findings underscore the pivotal role played by BIRC5 in regulating a wide range of biological behaviors such as cell cycle progression, DNA damage, DNA repair response, proliferation, and invasion within tumors. Experimental evidence further confirms that knockdown of BIRC5 effectively inhibits LUAD proliferation.

Conclusion

Our research systematically highlighted the profound association between BIRC5 expression and various clinical characteristics, survival, mutation patterns, and TME in many cancers. These analyses yield valuable perspectives on BIRC5’s function across different cancers.