Serum sphingosine-1-phosphate levels are associated with brain metastasis in -mutant lung adenocarcinoma.

Aim: To investigate the association between serum sphingosine-1-phosphate (S1P) levels and brain metastasis in EGFR-mutant lung adenocarcinoma (LUAD).

Methods: Serum S1P levels were analyzed in 103 LUAD patients. The baseline characteristics of the 103 patients in this study included the following: the overall cohort consisted of 50.49% males and 49.51% females. The average age of the cohort was 69.50 years (SD = 59.12). Regarding EGFR mutations, 52 patients (50.49%) had wild-type EGFR, 19 patients (18.45%) had EGFR Ex19Del, and 32 patients (31.07%) had the L858R mutation. Logistic regression models and competing risk Cox analyses were used to evaluate the association between S1P levels and brain metastasis. Kaplan-Meier curves assessed cumulative brain metastasis incidence over time.

Results: Serum sphingosine-1-phosphate (SIP) levels were measured with the following results (mean ± SD): wild-type EGFR, 970.44 ± 344.37 nmol/L; Ex19Del, 1,246.41 ± 306.93 nmol/L; and L858R, 1,333.21 ± 385.08 nmol/L ( < 0.001). In EGFR-mutant patients, S1P levels were independently associated with increased risk of brain metastasis (OR = 8.2, p = 0.003; HR = 105,  < 0.001), whereas no significant association was observed in EGFR wild-type patients. Kaplan-Meier analysis revealed that high S1P levels were linked to earlier brain metastasis in EGFR-mutant patients ( = 0.0034). The relationship between S1P levels and brain metastasis was not significantly influenced by the presence of bone metastasis ( > 0.1).

Conclusion: Elevated serum S1P levels are significantly associated with brain metastasis in EGFR-mutant LUAD patients. S1P may serve as a biomarker for brain metastasis risk and a potential therapeutic target.