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

## TL;DR

This study shows that low SALL1 levels in kidney cancer are linked to worse outcomes and may help predict treatment response and immune activity.

## Contribution

The study reveals SALL1 as a novel prognostic biomarker and potential therapeutic target in clear cell renal cell carcinoma.

## Key findings

- SALL1 is significantly downregulated in ccRCC tumors compared to normal tissues.
- Low SALL1 expression correlates with poor survival and is an independent prognostic factor.
- SALL1 enhances sensitivity to Sunitinib and modulates immune-related pathways.

## Abstract

Spalt-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.

We 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.

SALL1 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.

SALL1 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.