ArticleTranslational cancer research2026
Evaluation of the subtype-specific epigenetic prognostic association of HELLS in non-small cell lung cancer: integrated clinical and molecular insights.
Article in Translational cancer research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Helicase, lymphoid-specific (HELLS) is an epigenetic chromatin remodeler implicated in several cancers, but its prognostic role in non-small cell lung cancer (NSCLC) subtypes remains unclear. We investigated the expression, prognostic significance, and subtype-specific associations of HELLS in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Methods: The Cancer Genome Atlas (TCGA) and independent Gene Expression Omnibus (GEO) datasets were analyzed. HELLS expression was compared between tumor and normal tissues, survival was evaluated separately in LUAD and LUSC, and gene set enrichment analysis (GSEA) was performed. Multivariable analyses were used to assess associations between HELLS and selected oncogenic and immune-related genes after adjustment for clinical variables. Results: HELLS was significantly upregulated in both LUAD and LUSC compared with normal lung tissues (P<0.001). High HELLS expression was associated with shorter overall survival (OS) in LUAD (log-rank P=0.001) and in the TCGA-LUSC cohort (log-rank P=0.002); however, external validation in GSE42127 (LUSC, n=43) was not significant [log-rank P=0.12; hazard ratio (HR) =0.49, 95% confidence interval (CI): 0.20-1.22, P=0.13]. HELLS-high LUAD tumors showed enrichment trends enriched in proliferation-related pathways, whereas HELLS-low LUSC tumors were enriched in inflammatory and apoptotic pathways. HELLS expression remained associated with Conclusions: HELLS shows a subtype-dependent prognostic and molecular association in NSCLC, with the strongest and most reproducible signal in LUAD; however, its prognostic value is attenuated after multivariable adjustment and is not consistently reproduced across external cohorts.
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