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<p>Arachidonate 15-Lipoxygenase (ALOX15) has been implicated in cellular homeostasis, yet its pan-cancer expression patterns, clinical relevance, and molecular mechanisms remain incompletely characterized. This study comprehensively analyzed ALOX15 expression across 33 cancer types using multi-omics data to evaluate its role in tumor progression, diagnostic potential, and therapeutic implications. We integrated resources from TCGA, GTEx, and other public databases to assess ALOX15 expression, mutational status, diagnostic value, prognostic significance, immune infiltration, and potential relevance to chemotherapy and immunotherapy. Results showed that ALOX15 was downregulated in multiple cancers, including head and neck squamous cell carcinoma (HNSC), but upregulated in others such as liver cancer. Its expression exhibited both positive and negative correlations with prognosis depending on cancer type. Immune infiltration analysis revealed significant associations between ALOX15 and levels of B cells, CD8⁺ T cells, dendritic cells, and M1 macrophages in most tumors. Pathway analysis indicated a close relationship between ALOX15 and the ERK signaling pathway. Experimental validation in HNSC clinical samples and cell lines demonstrated that low ALOX15 expression was correlated with clinicopathological parameters and identified as a protective factor. Functional assays showed that ALOX15 overexpression suppressed malignant behavior in cancer cells. Western blot analysis further confirmed that ALOX15 inhibits HNSC progression via the ERK pathway. In summary, ALOX15 may serve as a potential biomarker across multiple cancer types.&#xa0;</p> Graphical abstract <p>This study conducted a comprehensive pan-cancer bioinformatic analysis of ALOX15 using databases including TCGA, GTEx, HPA, and cBioPortal, with experimental validation in head and neck squamous cell carcinoma (HNSC) at both tissue and cellular levels. Immunohistochemical staining confirmed the expression and prognostic value of ALOX15. Functional in vitro assays demonstrated that ALOX15 suppresses malignant behaviors in cancer cells, potentially through the ERK signaling pathway. These findings suggest ALOX15 as a potential biomarker in HNSC.</p> <p></p>

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ALOX15 exerts tumor-suppressive role in head and neck squamous cell carcinoma via ERK pathway

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月13日

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  • Aoran Liu,
  • Xinyue Zhang,
  • Ruipeng Li,
  • Yuzhe Zhang,
  • Ziyi Yang,
  • Dan Zou,
  • Xu Ji,
  • Hong Li

摘要

Arachidonate 15-Lipoxygenase (ALOX15) has been implicated in cellular homeostasis, yet its pan-cancer expression patterns, clinical relevance, and molecular mechanisms remain incompletely characterized. This study comprehensively analyzed ALOX15 expression across 33 cancer types using multi-omics data to evaluate its role in tumor progression, diagnostic potential, and therapeutic implications. We integrated resources from TCGA, GTEx, and other public databases to assess ALOX15 expression, mutational status, diagnostic value, prognostic significance, immune infiltration, and potential relevance to chemotherapy and immunotherapy. Results showed that ALOX15 was downregulated in multiple cancers, including head and neck squamous cell carcinoma (HNSC), but upregulated in others such as liver cancer. Its expression exhibited both positive and negative correlations with prognosis depending on cancer type. Immune infiltration analysis revealed significant associations between ALOX15 and levels of B cells, CD8⁺ T cells, dendritic cells, and M1 macrophages in most tumors. Pathway analysis indicated a close relationship between ALOX15 and the ERK signaling pathway. Experimental validation in HNSC clinical samples and cell lines demonstrated that low ALOX15 expression was correlated with clinicopathological parameters and identified as a protective factor. Functional assays showed that ALOX15 overexpression suppressed malignant behavior in cancer cells. Western blot analysis further confirmed that ALOX15 inhibits HNSC progression via the ERK pathway. In summary, ALOX15 may serve as a potential biomarker across multiple cancer types. 

Graphical abstract

This study conducted a comprehensive pan-cancer bioinformatic analysis of ALOX15 using databases including TCGA, GTEx, HPA, and cBioPortal, with experimental validation in head and neck squamous cell carcinoma (HNSC) at both tissue and cellular levels. Immunohistochemical staining confirmed the expression and prognostic value of ALOX15. Functional in vitro assays demonstrated that ALOX15 suppresses malignant behaviors in cancer cells, potentially through the ERK signaling pathway. These findings suggest ALOX15 as a potential biomarker in HNSC.