Prognostic Value of Exportin-7 and Its Association with KRAS Status and Autophagy Markers in Small Intestinal...

Small intestinal adenocarcinoma (SIAC) is a rare malignancy with a rising incidence and poor prognosis. Although exportin-7 (XPO7) is typically characterized as a tumor suppressor, recent evidence suggests context-dependent oncogenic functions, yet its role in SIAC remains unexplored. This study evaluated the clinicopathological significance of XPO7 expression and its association with KRAS status, autophagy, and cancer stemness in 191 surgically resected primary SIAC cases using immunohistochemistry and automated digital quantification. XPO7 was significantly upregulated in SIAC compared to normal mucosa (p < 0.001). High XPO7 expression, observed in 27.2% of cases, correlated with higher histological grade (p = 0.023) and was identified as an independent predictor of poor overall survival (hazard ratio = 1.703; p = 0.008). Subgroup analysis revealed that high XPO7 levels were associated with significantly shorter median overall survival specifically in cases featuring lymphovascular invasion, nodal metastasis, and KRAS mutations. Furthermore, XPO7 expression demonstrated a significant positive correlation with autophagy markers (LC3B and p62) but not with stemness markers (Sox2, Oct4, and Nanog). In conclusion, XPO7 serves as a significant independent prognostic biomarker for SIAC, and its correlation with autophagy markers in aggressive subgroups highlights its potential as a promising therapeutic target.