A Pan-Cancer Analysis of Ferroptosis-Related Gene Arachidonic Acid 15-Lipoxygenase-1 (ALOX15): Its Prognostic and Immunotherapeutic Values

Background. Emerging research has identified ferroptosis as a novel form of programmed cell death, and Arachidonic acid 15-lipoxygenase-1 (ALOX15) stands out as a pivotal gene in mediating this process. Nonetheless, the role of ALOX15 in human tumors remains elusive. Methods. We utilized TIMER 2.0 to investigate the differential expression profiles of ALOX15 between pan-cancer and normal tissues. Further data from the TCGA, GEPIA, UALCAN, HPA, and CPTAC databases were analyzed to verify the levels of mRNA, protein expression, and promoter methylation across various cancer types. The survival prognosis, clinical features, and genetic alterations of ALOX15 were also evaluated. GO/KEGG enrichment analyses and single-cell transcriptome sequencing were employed for functional enrichment analysis. The gene mutation of ALOX15 and its prognostic value were analyzed using the cBioPortal platform. Finally, the relationship between ALOX15 and immune cell infiltration, Immune Checkpoints (ICKs), genomic instability, and drug sensitivity was further explored using GSCA. Results. Our findings revealed that the transcription and protein expression of ALOX15 were significantly reduced in HNSC, LUAD, LUSC, SKCM, KICH, and THCA, while they were up-regulated in ESCA, LIHC, PRAD, and UCEC. Notably, the expression of ALOX15 had prognostic value for certain cancers, including LUAD, LUSC, LIHC, KIRC, HNSC, THCA, and LGG. Additionally, ALOX15 expression was markedly correlated with clinical characteristics, immune cell infiltration, ICKs, genomic instability, and antitumor drug sensitivity in various tumors. Gene mutations of ALOX15 and their prognostic value were discovered in pan-cancers. Furthermore, GO/KEGG analysis and single-cell transcriptome sequencing indicated that ALOX15 was significantly associated with cancer-related pathways. Conclusion. Our comprehensive pan-cancer analysis shed light on the role and significance of ALOX15, suggesting its potential as a prognostic and immunotherapeutic marker for pan-cancer. These findings may provide new directions and evidence for cancer therapeutics.