Transcriptomic profiling of sphingolipid-related gene expression in breast cancer

Abstract

Sphingolipid metabolism has a crucial role in regulation of cancer-linked cellular processes like apoptosis, cell proliferation. Despite increasing number of studies on sphingolipid pathway dysregulation particularly in breast cancer, comprehensive transcriptomic profiling of sphingolipid-metabolism genes incorporated with survival data remains scarce. The study profiles mRNA expression of 46 sphingolipid-metabolism genes in breast cancer, assesses association with clinical features and evaluates them as potential prognostic markers through survival model. RNA-sequencing data from The Cancer Genome Atlas Breast Cancer dataset (TCGA-BRCA) was retrieved and secondary analysis was performed. Statistical analyses including one-sample t-test for differential expression, one-way ANOVA for stage- and gender-specific analyses, Kaplan-Meier plotting with log-rank testing for survival stratification as well as Cox proportional hazards regression for multivariate prognostic modeling were utilized. Spearman correlation was also used for co-expression evaluation among candidate genes. Out of 47 examined genes, 44 showed statistically significant differentiation from normal breast tissue (p < 0.05). Six genes – KDSR, CERS4, CERS5, DEGS2, PLPP1, and NEU1 demonstrated statistically meaningful stage-associated expression differences by ANOVA even though effect sizes were small (ω² = 0.007-0.036). Gender-associated expression differences were showed by five genes. CERS4, CERS5, DEGS2, and NEU1 were identified as significant protective factors (HR = 0.819–0.899, p < 0.05) through age- and stage-adjusted Cox proportional hazards regression model. The findings indicate that sphingolipid-metabolism gene expression reveals a context-dependent prognostic effect in breast cancer, which becomes biologically important in younger patients and earlier disease stages.