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Comprehensive analysis of SYTL4 differential expression and clinical implications in DLBCL
1Department of Cardio-Pulmonary Function, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Background:
Diffuse large B-cell lymphoma (DLBCL), a common type of non-Hodgkin lymphoma (NHL), is associated with heterogeneous clinical outcomes, with a subset of patients experiencing refractory disease or relapse, underscoring the need for novel biomarkers to refine risk stratification. This study aimed to investigate the biological role and clinical significance of synaptotagmin-like 4 (SYTL4) in DLBCL.
Methods:
RNA-seq data from TCGA and GTEx were normalized (TPM) and log2-transformed. Survival analysis stratified patients based on the median SYTL4 expression level (cutoff = 0.304), with Kaplan-Meier curves and Cox regression analysis performed. Differentially expressed genes (|log2FC|>1, FDR<0.05) underwent functional annotation (GOKEGG, GSEA) and PPI network constructed. Immune infiltration was assessed via ssGSEA. Formalin-fixed paraffin-embedded (FFPE) tissue blocks from testicular DLBCL patients were obtained. A tissue microarray was constructed. Immunohistochemistry with anti-SYTL4 antibody was performed, and digital images were scored semi-quantitatively (0-3+) by two pathologists.
Results:
RNA-seq analysis revealed a significant upregulation of SYTL4 expression in DLBCL patients compared to healthy donors, observed in both tissue and peripheral blood samples, a finding further validated by immunohistochemical staining. Survival analysis revealed that elevated SYTL4 expression was correlated with an unfavorable prognosis (P = 0.037), and multivariate Cox regression confirmed that high SYTL4 expression was an independent prognostic factor (HR = 25.541, P = 0.017). Differential gene screening identified 1,074 differentially expressed genes, including 628 upregulated genes and 446 downregulated genes. Enrichment analysis revealed a significant association of SYTL4-related genes with pathways involved in cell-cell adhesion and the immune response. Protein‒protein interaction (PPI) network analysis revealed interactions between SYTL4 and key regulators such as phosphatase and actin regulator 2 (PHACTR2), suggesting its potential role in DLBCL progression.
Conclusion:
These findings highlight the potential of SYTL4 as a promising diagnostic marker, prognostic biomarker, and therapeutic target. Further exploration of its applicability in immunotherapy may lead to the development of personalized treatment strategies for DLBCL patients.
