Comprehensive multi-omics analysis of the prognostic value and immune signature of NCF2 in pan-cancer and its relationship with acute myeloid leukemia.

Background: The neutrophil cytoplasmic factor 2 (NCF2) gene encodes the p67phox protein, which has been implicated in the pathogenesis of several diseases. However, its specific role in tumorigenesis remains ambiguous. This study seeks to clarify the prognostic implications, immune profile, and therapeutic responses associated with NCF2 across different cancer types.

Methods: We conducted a comprehensive analysis using multi-omics data to investigate tissue-specific and single-cell specific expression, pan-cancer expression patterns, epigenetic modifications, the immune microenvironment, and therapeutic responses. Our study specifically examined NCF2-associated immune signatures, molecular mechanisms, and potential therapeutic targets in acute myeloid leukemia (AML). Additionally, we performed in vitro experiments to assess how NCF2 knockdown influences cell proliferation, apoptosis, and cell cycle dynamics in AML cell lines U937 and KG-1.

Results: NCF2 is dysregulated in more than two-thirds of cancer types, with elevated expression strongly correlating with poor prognosis in various cancers, including leukemia. Multifactorial Cox analysis has identified NCF2 as an independent prognostic factor for leukemia. Immunological studies have highlighted NCF2's impact on the tumor microenvironment, particularly affecting monocytes and macrophages. Furthermore, NCF2 expression closely correlates with responses to immunotherapy and chemotherapy. In vitro experiments demonstrate that NCF2 knockdown alters proliferation, apoptosis, and cell cycle dynamics of U937 cells and KG-1 cells. Notably, NCF2 is involved in regulating the differentiation of monocytes into macrophages.

Conclusions: These findings highlight NCF2 as a promising pan-cancer biomarker that significantly impacts tumor microenvironment, therapeutic response, and is critically associated with cell cycle regulation, apoptosis and macrophage transformation in AML.