Pan-cancer analysis of the oncogenic role of ZNF703 in regulating tumor immunity

ZNF703, a member of the NET/NLZ family, plays a critical role in individual development and cancer progression. Despite its significance, a comprehensive pan-cancer analysis of ZNF703 remains underexplored. In this study, we performed a systematic pan-cancer analysis to elucidate the mechanistic and functional roles of ZNF703 in tumorigenesis. Our findings reveal that elevated ZNF703 expression is significantly correlated with cancer progression, adverse clinical outcomes, and the enrichment of immune cells within the tumor microenvironment (TME), particularly cancer-associated fibroblasts (CAFs), CD8⁺ T cells, and M2 macrophages, suggesting its pivotal role in modulating tumor immunity. Mechanistically, ZNF703 regulates tumor immunity by binding to promoter sequences, thereby suppressing the expression of CD274, ICAM1, and CXCL3, which may facilitate tumor immune escape. Additionally, we identified functional hub genes associated with ZNF703, including DDHD2, LSM1, and BAG4. Notably, ZNF703, DDHD2, LSM1, and BAG4 are co-localized within the amplicons at the chromosome 8p11-p12 region, indicating a potential cooperative role in driving cancer initiation and progression. Collectively, these findings underscore the essential roles of ZNF703 in cancer development, patient prognosis, and the regulation of anti-tumor immunity, highlighting its potential as a biomarker for cancer detection and as a novel immunotherapeutic target.