Pan-cancer expression and clinical associations of HSD11B2 and its functional role in breast cancer cells
Year: 2026
Type: article
Abstract: Although HSD11B2 serves as a crucial enzyme governing glucocorticoid metabolism, its systemic roles across human malignancies have not been fully elucidated. Current evidence remains fragmented, and integrative pan-cancer investigations covering its expression control, clinical relevance, immune correlates and influence on breast cancer aggressiveness are still lacking. To fill this gap, we integrated multi-omics bioinformatic analyses with experimental validation at both the cellular and animal levels, thereby systematically assessing the diagnostic and prognostic significance, underlying molecular mechanisms and tumor-promoting activities of HSD11B2 in breast cancer. Our ultimate goal was to establish HSD11B2 as an indicator usable for pan-cancer diagnosis and prognosis, and to explore its potential as a candidate therapeutic target in breast oncology. Publicly available transcriptomic and clinical datasets, chiefly from TCGA and GTEx, were collected and merged. Using the R computing environment together with multiple multi-omics bioinformatics platforms, we characterized the HSD11B2 expression landscape, its prognostic and diagnostic significance, genetic alterations, epigenetic control, immune infiltration patterns and associated functional pathways across pan-cancer cohorts. How HSD11B2 regulates the proliferative, migratory and invasive behaviors of breast cancer cells was then examined experimentally, using qRT-PCR, Western blotting and immunohistochemistry together with CCK-8, colony formation, Transwell and wound healing assays and a nude mouse subcutaneous xenograft model. HSD11B2 showed broad expression disturbance across the pan-cancer spectrum, being markedly elevated in tumors such as BRCA, CHOL and LIHC but evidently reduced in COAD, KIRC, THCA and additional malignancies. Its transcript level showed significant prognostic associations in eight cancer types and acted as an independent outcome predictor in five of them, and the nomogram built on these variables achieved satisfactory predictive accuracy. Moreover, HSD11B2 transcripts distinguished malignant from normal tissues with excellent accuracy (AUC > 0.9) for CHOL, COAD, KIRC, KIRP and READ. At the regulatory level, HSD11B2 abundance was associated with copy number gain, promoter hypomethylation and m6A regulatory signatures. Tumors with abundant HSD11B2 displayed an immune-desert “cold tumor” phenotype, tightly linked to an immunosuppressive microenvironment. Enrichment analyses connected HSD11B2 predominantly to steroid hormone metabolism, cell-proliferation and immune-regulation pathways. Cellular and animal experiments consistently demonstrated that silencing HSD11B2 markedly weakened the proliferative, migratory and invasive capacities of breast cancer cells in vitro, and xenograft tumors in nude mice grew more slowly upon HSD11B2 knockdown. HSD11B2 holds important clinical significance for prognosis assessment and diagnosis across pan-cancer settings. Through multi-dimensional regulatory control it participates in tumor progression and displays oncogenic activity in breast cancer. Collectively, HSD11B2 represents a promising indicator for pan-cancer diagnosis and prognosis, as well as a potential therapeutic target against this malignancy.
Source: Scientific Reports
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
OpenAlex ID: W7225735203
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