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

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.