SGO1 and SGO2 are Associated With Disease Progression and an Immunosuppressive Microenvironment in Papillary Renal Cell Carcinoma.

BACKGROUND

Shugoshin proteins SGO1 and SGO2 regulate chromosome cohesion and segregation during mitosis and meiosis, and their aberrant expression is implicated in several cancers. However, the mechanistic involvement of these two proteins in papillary renal cell carcinoma (KIRP) and their contribution to immune evasion remains unclear. Therefore, in the present study, we aimed to determine SGO1 and SGO2 expression patterns and prognostic significance, clarify their functional involvement in driving tumor progression, and evaluate their impact on the tumor immune microenvironment.

METHODS

We performed an integrative analysis using multi-omics datasets retrieved from TCGA, GTEx, and GEO, complemented by single-cell transcriptomics, immunohistochemistry of patient samples, and functional assays in renal cancer cell lines. We also investigated the expression, clinical relevance, and mechanistic roles of SGO1 and SGO2 in KIRP progression and tumor immune regulation.

RESULTS

SGO1 and SGO2 were significantly upregulated in KIRP, correlating with advanced tumor stage and poor overall survival. Receiver operating characteristic analyses demonstrated strong diagnostic performance, particularly when SGO1 and SGO2 were evaluated jointly. Functional knockdown experiments revealed that both SGO1 and SGO2 promote the proliferation, migration, and invasion of renal cancer cells. Gene enrichment analyses further linked these proteins to E2F signaling, genomic stability, and immune-related pathways. Importantly, high SGO1 and SGO2 expression was strongly associated with increased infiltration of immunosuppressive cells, including regulatory T cells, M2 macrophages, cancer-associated fibroblasts, and myeloid-derived suppressor cells, suggesting their potential contribution to an immune-evasive tumor microenvironment.

CONCLUSIONS

SGO1 and SGO2 are associated with aggressive tumor biology in papillary renal cell carcinoma and correlate with remodeling of the tumor immune microenvironment toward an immunosuppressive state. Importantly, while these findings highlight a strong association with the tumor immune microenvironment, they remain correlative, and further mechanistic studies are warranted to establish a direct causal relationship. Nevertheless, their associations with both tumor progression and immunosuppressive features suggest potential as prognostic biomarkers and targets for future mechanistic studies.