Comprehensive Pan-Cancer Study Identifies Hepatic Leukemia Factor as a Crucial Biomarker for Immunity and Prognostic Accuracy

Background The circadian gene hepatic leukemia factor (HLF), a proline and acidic amino acid-rich basic leucine zipper (PAR bZIP) transcription factor, is under-explored in terms of its prognostic and immunotherapeutic roles across various cancers. Methods Utilizing databases like UCSC Xena, TIMER2.0, and TCGA, this study assessed HLF's expression variability across numerous cancer forms. The research further assessed the survival outcomes, clinical attributes, and genetic alterations associated with HLF. Additionally, the impact of HLF on immunotherapy outcomes was analyzed through methodologies such as Gene Set Enrichment Analysis, evaluation of the tumor microenvironment, and immune cell infiltration studies. Results Findings indicate a notable reduction in HLF's transcription and protein levels in most cancers, highlighting its prognostic relevance for patient survival in specific cancers like CESC, HNSC, KIRC, KIRP, LGG, LUAD, MESO, PAAD, and READ. Furthermore, in certain cancers, a significant correlation between HLF expression and tumor mutation burden (TMB), microsatellite instability (MSI), and clinical features was observed. Gene Set Enrichment Analysis revealed significant links between HLF and immune-related pathways. The study also confirmed a strong association between HLF expression and the infiltration of immune cells, as well as its correlation with chemotherapy resistance-related genes, genes related to immune microenvironment reprogramming, and genes related to carbohydrate metabolism. The biological function of HLF was verified in common lung cancer cell lines. Knockdown of HLF enhanced the proliferation and migration abilities of tumor cells, while overexpression inhibited these abilities. Conclusions This comprehensive investigation underscores the potential of HLF as a valuable prognostic and immunotherapeutic biomarker in pan-cancer, offering novel insights and evidence for enhancing cancer treatment strategies.