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Pan-cancer analysis of the oncogenic role of SRY-related high-mobility group box protein B5 in human tumors.

Experimental and therapeutic medicine 2026 Vol.31(2) p. 32

Tong Y, Da H, Tang K, Zhou Q, Liu S, Yin L, Long L, Bai S, Ou L, Yin Q

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SRY-related high-mobility group protein B5 (SOX5) functions as an oncogene in diverse human malignancies, contributing to tumor progression, metastasis and therapy resistance across various cancer typ

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APA Tong Y, Da H, et al. (2026). Pan-cancer analysis of the oncogenic role of SRY-related high-mobility group box protein B5 in human tumors.. Experimental and therapeutic medicine, 31(2), 32. https://doi.org/10.3892/etm.2025.13027
MLA Tong Y, et al.. "Pan-cancer analysis of the oncogenic role of SRY-related high-mobility group box protein B5 in human tumors.." Experimental and therapeutic medicine, vol. 31, no. 2, 2026, pp. 32.
PMID 41383256

Abstract

SRY-related high-mobility group protein B5 (SOX5) functions as an oncogene in diverse human malignancies, contributing to tumor progression, metastasis and therapy resistance across various cancer types. In light of this, a pan-cancer analysis was performed in the present study to investigate the oncogenic function of SOX5 in various human malignancies. SOX5 mRNA expression levels were compared between normal and malignant tissues using The Cancer Genome Atlas database and diagnostic effectiveness was evaluated using receiver operating characteristic curve analysis. Kaplan-Meier survival analysis was performed to investigate the association between SOX5 expression and overall survival, disease-specific survival, disease-free interval and progression-free interval. The influence of SOX5 on immune infiltration and immunological scores in the tumor microenvironment was assessed utilizing Estimation of Stromal and Immune Cells in Malignant Tumor Tissues Using Expression Data, Cell-Type Identification by Estimating Relative Subsets of RNA Transcripts and single-sample Gene Set Enrichment Analysis methodologies, in conjunction with its relationship to drug sensitivity and genetic modifications. SOX5 exhibited tissue-specific dysregulation, being markedly downregulated in carcinomas such as lung adenocarcinoma (LUAD), lung squamous cell carcinoma and breast cancer, while increased in testicular germ cell tumor and non-small cell lung cancer (NSCLC) cell lines. It demonstrated notable diagnostic potential, with good performance in LUAD (area under the curve=0.916). The prognostic relevance of SOX5 was contingent upon context as lower expression conferred protection in specific malignancies; however, it was associated with worse outcomes in others, such as low-grade glioma and pancreatic adenocarcinoma. Increased SOX5 expression was associated with an immunosuppressive milieu marked by a rise in regulatory T cells, a decline in cytotoxic T cells and the activation of immunological checkpoints including programmed death-ligand 1 and cytotoxic T lymphocyte associated protein 4. Moreover, SOX5 was associated with genomic instability, susceptibility to medicines such as azacitidine and distinct mutation patterns. SOX5 suppression in NSCLC cells impeded proliferation, migration and invasion. These findings collectively emphasize the key function of SOX5 in tumor biology and highlight its potential as a biomarker for cancer diagnosis, prognosis and therapeutic targeting.

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