ATG16L2 as a prognostic biomarker and therapeutic target in kidney renal clear cell carcinoma

Abstract

Kidney renal clear cell carcinoma (KIRC) carries substantial clinical challenges. This study examined ATG16L2 , an autophagy-related gene family member, across TCGA, CPTAC, GEO, and an independent cohort to assess its expression patterns, clinicopathological associations, and prognostic relevance. Immune landscapes were characterized through CIBERSORT, ESTIMATE, xCell, and single-cell analyses. Functional investigations employed shRNA-mediated knockdown in KIRC cell lines and xenograft models, with attention to the Notch signaling pathway. ATG16L2 was elevated in KIRC and associated with advanced disease and poorer survival. Its expression correlated with altered immune infiltration and immune checkpoint levels. Silencing ATG16L2 attenuated proliferative, migratory, and invasive capacities, partly through Notch pathway modulation. These findings position ATG16L2 as a prognostic indicator and immune microenvironment modulator in KIRC, with implications for therapeutic strategies targeting the ATG16L2-Notch axis.