Pan-cancer analysis identifies KANSL2 as a cell-cycle-associated regulator of tumor progression and immunity in liver hepatocellular carcinoma.

KANSL2, a core component of the NSL histone acetyltransferase complex, has been implicated in tumorigenesis. However, its pan-cancer relevance and functional role in liver hepatocellular carcinoma (LIHC) remain unclear. Multi-omics data from TCGA, GEO, and HPA were integrated to systematically evaluate KANSL2 expression, clinical significance, genomic alterations, and immune associations across cancers. Functional enrichment, immune infiltration analyses, and single-cell transcriptomics were performed. In vitro assays were conducted to validate the biological effects of KANSL2 in LIHC cells. KANSL2 is broadly upregulated across cancers and exhibits strong diagnostic performance. Elevated KANSL2 expression correlates with unfavorable prognosis, particularly in LIHC. Mechanistically, KANSL2 and its co-expressed genes are enriched in cell-cycle progression. KANSL2 expression is also closely associated with immune infiltration and immunoregulatory signaling within the tumor microenvironment, with single-cell data indicating preferential expression in proliferative T-cell subsets. Functional experiments demonstrate that KANSL2 silencing suppresses proliferation, migration, and invasion, and induces G2/M phase arrest in LIHC cells. Notably, its effects on apoptosis are limited, suggesting that KANSL2 primarily drives tumor progression through cell-cycle-dependent mechanisms. This study identifies KANSL2 as a key regulator of tumor progression and immune remodeling in LIHC. By promoting malignancy predominantly via cell-cycle control, KANSL2 represents a promising biomarker for diagnosis and prognosis, and a potential therapeutic target.