A pan-cancer analysis identifies HDAC11 as an immunological and prognostic biomarker

Histone deacetylase 11 (HDAC11) is aberrantly expressed in many types of cancer, and such abnormalities are associated with tumor immunity and heterogeneous clinical outcomes. Here, we explore the prognostic value and immunological function of HDAC11 across 33 cancer types. We observe HDAC11 is aberrantly expressed in 25 cancer types and positively or negatively associated with prognosis in different cancers. HDAC11 played a protective prognostic role in KIRP, KIRC, LGG, PCPG, READ, and UVM, which was contrary to the conventional opinion that HDAC11 was an oncogenic gene. Moreover, HDAC11 is negatively associated with tumor immune components, most immune checkpoint genes, and key cytokine expression. HDAC11 is correlated with tumor mutational burden in 11 cancer types and with microsatellite instability in 9 cancer types, suggesting HDAC11 may affect a patient's response to immune checkpoint inhibitor (ICI) therapy. In addition, HDAC11 is negatively correlated with the drug sensitivity of oxaliplatin, carmustine, ifosfamide, imexon, lomustine, and BN-2629, indicating the potential synergy between HDAC11 inhibitors and these anti-tumor drugs. In vitro assays indicate that HDAC11 inhibitor SIS17 combined with oxaliplatin shows a synergistic cytotoxic role in K562 cells while SIS17 has an antagonistic effect on the cytotoxic role of oxaliplatin in 769P cells. HDAC11 is also associated with hallmark pathways, including epithelial mesenchymal transition, IL-6/JAK/STAT3, and allograft rejection pathways. Overall, we provide clues regarding the key role of HDAC11 in multiple cancers.