Abstract
Esophageal cancer is the seventh leading cause of cancer-related deaths, with most cases diagnosed at locally advanced stages. Chemoradiotherapy is one of the most effective treatments for these patients. However, high rates of recurrence persist, highlighting the need for more reliable prognostic biomarkers. In this study, we identified immune-related prognostic genes through bulk (n = 119) and single-cell (n = 60) transcriptomic analyses. We then used Western blotting, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence to preliminarily investigate the potential biological functions of the candidate biomarker. The clinical prognostic utility of the candidate biomarker was validated in an independent cohort (n = 91) via ELISA of serum samples collected before and during chemoradiotherapy. The results showed that low expression of the secretory leukocyte peptidase inhibitor (SLPI) significantly correlated with tumor progression and poor prognosis. In epithelial cells, reduced SLPI expression was associated with decreased activation of differentiation-related pathways. Furthermore, SLPI expression levels were found to influence fibroblast phenotypes, with exogenous SLPI inhibiting the NF-κB pathway and restoring fibroblast quiescence. The results of ELISA showed that dynamic changes in serum SLPI levels during chemoradiotherapy serve as an independent prognostic factor. In conclusion, serum SLPI levels represent an easy-to-detect biomarker for dynamically monitoring the efficacy of chemoradiotherapy.