J Thorac Dis. 2026 Apr 30. 18(4):
353
Background: Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor characterized by rapid progression, early metastasis, and high mortality, with limited effective long-term treatment options. B4GALT1, a β-1,4-galactosyltransferase, has been implicated in the malignant progression of various cancers, but its specific role and underlying mechanisms in SCLC remain largely unexplored. We conducted a multi-omics analysis and clinical sample study to explore the function of B4GALT1 in SCLC.
Methods: This study comprehensively investigated the expression pattern, functional significance, and clinical relevance of B4GALT1 in SCLC. We conducted multi-omics analyses, including single-cell data processing, InferCNV analysis, and immune infiltration analysis, to explore the association between B4GALT1 and the immune microenvironment of SCLC and patient survival. To determine B4GALT1 as a potential circulating biomarker, quantitative data-independent acquisition (DIA) proteomics analysis was performed on serum samples from SCLC patients and healthy controls. Enzyme-linked immunosorbent assay (ELISA) was used to further verify the differential expression of serum B4GALT1 in a larger cohort of SCLC patients, to evaluate its diagnostic, prognostic, and treatment response predictive value.
Results: Multi-omics analysis revealed that B4GALT1 expression was significantly associated with patient survival. The expression of B4GALT1 positively correlated with macrophage infiltration in the tumor and negatively correlated with CD4+ T cells in the tumor. There was a negative correlation in inactivated naïve B cells, eosinophils, and CD4 naïve T cells, while it showed a positive correlation in dendritic cells, M0/M1/M2 macrophages, natural killer (NK) cells, CD8 T cells, follicular helper T cells, and regulatory T cells. ELISA results showed that serum protein B4GALT1 expression was higher in patients with SCLC than in healthy controls. Elevated serum B4GALT1 protein levels correlated with poor treatment outcomes in patients with SCLC undergoing chemoradiotherapy.
Conclusions: Our findings establish B4GALT1 as a critical prognostic, diagnostic, and predictive biomarker in SCLC, with its expression closely linked to the tumor immune microenvironment and treatment response. Targeting B4GALT1 or its related pathways may represent a novel therapeutic strategy, and serum B4GALT1 holds promise as a liquid biopsy marker for SCLC patient stratification, monitoring, and guiding treatment decisions.
Keywords: B4GALT1; biomarker; liquid chromatography-tandem mass spectrometry (LC-MS/MS); programmed death-1 (PD-1); small cell lung cancer (SCLC)