AUTHOR=Qu Gen-Yi , Chen Shao-Hao , Liu Meng-Xin , Wang Yi-Jie , Long Zhao-Hui , Xu Ning , Xue Xue-Yi 

TITLE=Downregulation of SALL1 and its association with poor prognosis and the immune cell landscape in clear cell renal cell carcinoma

JOURNAL=Frontiers in Oncology

VOLUME=Volume 15 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1624651

DOI=10.3389/fonc.2025.1624651

ISSN=2234-943X

ABSTRACT=BackgroundSpalt-like transcription factor 1 (SALL1), a member of the Krüppel-associated box-containing zinc finger proteins, has been implicated in tumor suppression, epigenetic regulation, and immune modulation in several malignancies. However, its role in clear cell renal cell carcinoma (ccRCC) remains poorly understood. This study aims to comprehensively assess the clinical significance, immunological relevance, and potential therapeutic value of SALL1 in ccRCC.MethodsWe analyzed transcriptomic and clinical data from public databases to explore the expression, prognostic value, and clinical correlations of SALL1 in ccRCC. The immune cell landscape associated with SALL1 was assessed using various immune algorithms. SALL1 expression in ccRCC tissues and cells was validated by immunohistochemistry (IHC), RT-qPCR, and Western blot analyses. Gene Ontology and KEGG pathway analyses were employed to identify the potential biological functions of SALL1. Functional assays, including MTT, colony formation, and Transwell assays, were performed to evaluate the effects of SALL1 on ccRCC cell proliferation, invasion, and migration. In vivo xenograft models using nude mice further supported these findings. We also conducted drug sensitivity analyses using bioinformatic prediction and validated the enhanced sensitivity to Sunitinib in SALL1-overexpressing ccRCC cells through a dose-dependent CCK-8 assay.ResultsSALL1 expression was significantly downregulated in ccRCC tumors compared to normal tissues. Overexpression of SALL1 inhibited cell proliferation, migration, and invasion in A498 and 769-P cell lines. Survival analysis revealed that low SALL1 expression was associated with poor overall survival, progression-free survival, and disease-specific survival. Univariate and multivariate Cox regression analyses confirmed that SALL1 expression is an independent prognostic factor for ccRCC. Functional enrichment analyses indicated that genes associated with SALL1 were enriched in pathways related to ion transport and immune modulation. Furthermore, SALL1 also exhibited positive correlations with the sensitivity to multiple anticancer agents.ConclusionsSALL1 is significantly downregulated in ccRCC and independently predicts poor clinical outcomes. It exerts tumor-suppressive effects and is involved in shaping an immunologically favorable tumor microenvironment. Functional assays confirmed its ability to enhance drug responsiveness, especially to Sunitinib. These findings suggest that SALL1 may serve as a prognostic biomarker and a potential modulator of immune and therapeutic responses in ccRCC.