Lipocalin-2 as a prognostic biomarker and its association with systemic inflammation in small cell lung cancer

Abstract

BackgroundSystemic inflammation is believed to contribute to small cell lung cancer (SCLC) progression, but the underlying relationship remains unclear. Lipocalin-2, a potential biomarker of inflammation, has been implicated in various cancers but its prognostic value in SCLC is underexplored.MethodsWe retrospectively analyzed 191 patients with SCLC (72 with limited-stage [LD] and 119 with extensive-stage) treated using platinum-based chemotherapy. Lipocalin-2 expression was evaluated using immunohistochemistry. Optimal cutoff values for lipocalin-2 and neutrophil-to-lymphocyte ratio (NLR) were determined using time-dependent receiver operating characteristic curve analysis. The pectoralis muscle index was used to assess sarcopenia.ResultsIn LD-SCLC, high lipocalin-2 expression was associated with worse progression-free survival (PFS; median: 7.0 vs. 15.9 months, p = 0.015) and overall survival (OS; median: 12.9 vs. 30.3 months, p = 0.035) compared with low lipocalin-2 expression. Patients were stratified into three prognostic groups by combining lipocalin-2 with NLR: low lipocalin-2/low NLR, high lipocalin-2/low NLR or low lipocalin-2/high NLR, and high lipocalin-2/high NLR (median PFS: 17.3 vs. 11.0 vs. 6.3 months, p = 0.004; median OS: 30.5 vs. 17.3 vs. 8.6 months, p = 0.002). Similar trends were observed when combining lipocalin-2 with the pectoralis muscle index. High lipocalin-2 expression was also associated with lower complete response rates (18.9% vs. 34.3%, p = 0.035). No significant prognostic implications were found for lipocalin-2 in extensive-stage SCLC.ConclusionsHigh lipocalin-2 expression is potentially associated with poorer survival in LD-SCLC. Combining lipocalin-2 with other inflammation-related markers could improve prognostic stratification. High lipocalin-2 expression is associated with poorer progression-free and overall survival in limited-stage small cell lung cancer (LD-SCLC). Combining lipocalin-2 with neutrophil-to-lymphocyte ratio or pectoralis muscle index enhances prognostic stratification, suggesting its potential utility as a biomarker in LD-SCLC. No significant prognostic implications were found for lipocalin-2 in extensive-stage SCLC. image