High SOX17 expression is correlated with favorable prognosis and CD8(+) TILs expression in patients with pancreatic cancer after curative resection.

The SRY-box transcription factor 17 (SOX17) plays a critical role in tumorigenesis and tumor progression and reshaping the tumor immune ecosystem in several cancer types, but its role in pancreatic cancer (PC) remains unknown. A total of 168 patients with PC who underwent curative resection were consecutively enrolled, and immunohistochemical (IHC) staining was performed, followed by Kaplan-Meier and Cox proportional hazards regression analyses. Meanwhile, specific markers of cancer-associated fibroblasts (CAFs) and tumor-infiltrating lymphocytes (TILs) and PD-L1 expression were detected by IHC staining, and their correlation with SOX17 were evaluated. Finally, single-cell and bulk RNA-seq analyses of public datasets were used to validate the expression profile of SOX17 in PC. The Kaplan-Meier curve showed that high SOX17 expression was correlated with a longer overall survival (OS) and disease-free survival (DFS) in patients with PC. Univariate (hazard ratio [HR] = 0.593, P = 0.005 for OS; HR = 0.602, P = 0.012 for DFS) and multivariate (HR = 0.662, P = 0.042 for OS; HR = 0.602, P = 0.036 for DFS) Cox regression analyses demonstrated that high SOX17 expression was an independent favorable prognostic factor. The correlation analysis showed that SOX17 expression was correlated with the expression of CD8+ TILs (P = 0.012) and FAP+ CAFs (P = 0.011). The correlations between SOX17 and CD8+ TILs were validated by multiple algorithms through single-cell and bulk RNA-seq analyses. The present study demonstrates that SOX17 serves as a significant prognostic marker and reflects the tumor immune ecosystem in pancreatic cancer.