Background Thymocyte selection-associated HMG-BOX (TOX) belongs to a family of transcription factors containing a highly conserved region of the high mobility group box (HMG-Box). A growing body of research has shown that TOX is involved in the occurrence and development of tumors and promotes T-cell exhaustion. We assessed the role of TOX with The Cancer Genome Atlas (TCGA) Pancancer Data. Methods TOX expression was examined with RNA-seq data from the TCGA and Genotype-Tissue Expression (GTEx) databases. The genetic alteration status and protein level of TOX were analyzed using databases, including the Human Protein Atlas (HPA), GeneCards, and STRING. The prognostic significance was estimated with survival data from the TCGA. Moreover, R software was used for enrichment analysis of TOX. The relationship between TOX and immune cell infiltration was assessed with the Tumor Immune Estimation Resource (TIMER) 2.0 database and the “CIBERSORT” method. The correlation between TOX and immune checkpoints was further explored. Immunohistochemical analysis was used to further verify the difference in TOX expression between cancerous and paracancerous tissues, and cell viability was evaluated using a CCK-8 assay. Results In most cancer types in the TCGA cohort, differential TOX expression was observed. The genetic alteration status and protein level of TOX were examined, and the prognosis of cancers was associated with TOX expression. Moreover, TOX levels were closely related to different immune-related pathways, immune cell infiltration and immune checkpoints. Additionally, significant differences in TOX expression between several cancerous and paracancerous tissues were validated. Furthermore, TOX clearly impacted the viability of cancer cells. Conclusions TOX, a potential biomarker for cancer, may be involved in the regulation of the immune microenvironment and can be used for new targeted drugs.

Background TOX (Thymocyte Selection-Associated HMG BOX) belongs to a family of transcription factors with a conserved high mobility group box (HMG-box) domain. Research indicates that TOX is involved in tumor development and T cell exhaustion. This study used data from The Cancer Genome Atlas (TCGA) to evaluate TOX expression across cancers. Methods TOX expression was analyzed using RNAseq data from TCGA and the Genotype-Tissue Expression (GTEx) database. Genetic alterations and protein levels were assessed via Human Protein Atlas (HPA), GeneCards, and String databases. Prognostic significance was determined using Kaplan-Meier analysis and univariate Cox regression. Enrichment analysis was performed using the "clusterProfiler" R package. The relationship between TOX and immune cell infiltration was analyzed via TIMER2 and "CIBERSORT." Differences in TOX expression between cancerous and adjacent normal tissues were confirmed using immunohistochemistry. Results TOX expression varied across TCGA cancer types, with high expression in gliomas and lymphoma and low expression in other cancers. Genetic alterations and protein levels correlated with cancer prognosis and were linked to immune pathways, cell infiltration, and checkpoints. Significant differences in TOX expression between cancerous and adjacent normal tissues were confirmed. Conclusions TOX is a promising biomarker for cancer, likely playing a role in regulating the immune microenvironment and providing opportunities for novel targeted therapies.