Study of Clinical Predictive Value and Immune Characterization of SLFN11 in Clear Cell Renal Cell Carcinoma

Abstract

Background: SLFN11 has been found to regulate the development and progression of a variety of cancers and is associated with drug therapy, while its role in clear cell renal cell carcinoma (ccRCC) remains unclear; therefore, the aim of this study was to investigate SLFN11 expression in ccRCC patients and its correlations with clinicopathological and immunological features. Methods: Gene profiles of ccRCC and the clinicopathological information of patients were downloaded from the TCGA database. Microarrays from the GEO database were used as a validation set for SLFN11 expression, which was experimentally verified in renal cancer cell lines by quantitative polymerase chain reaction (qPCR); protein expression and methylation levels were obtained from the HPA database and the UALCAN database. ROC curves, Kaplan-Meier survival analysis and Cox analysis were used to assess the diagnostic and predictive value of SLFN11 in ccRCC. Protein-protein interaction (PPI) networks for SLFN11 were obtained from the STRING website, and the TISIDB and TIMER 2.0 databases were used to study the relationship between SLFN11 and immune infiltration in the tumour microenvironment (TME). Results: SLFN11 was significantly overexpressed in ccRCC tissues and renal cancer cell lines, which may be closely related to its hypermethylation status (P < 0.001). SLFN11 was positively correlated with a highly aggressive disease state, with the ROC curve showing an AUC value of 0.910 for SLFN11 in diagnosing ccRCC, and Kaplan-Meier and Cox analyses also revealed that upregulation of SLFN11 predicted a poor prognosis for ccRCC patients (P < 0.05). In addition, enrichment analysis showed that SLFN11 was closely associated with immune-related signalling pathways, and further exploration comprehensively demonstrated strong positive correlations with tumour immune lymphocytes, immune checkpoint genes, chemokines and chemokine receptors. Conclusion: Overall, our data analysis shows that SLFN11 is a strong diagnostic and prognostic biomarker for ccRCC and is also associated with immune infiltration in the TME.

Schlafens: Emerging Therapeutic Targets

“…Additionally, Liu et al correlated the increased expression of immune checkpoint genes CTLA4 and CD244 with SLFN11. These associations indicate immune regulatory roles for SLFN11 that may have clinical translational implications for cancers suffering from immunosuppressive microenvironment [44].…”

“…Recently, SLFN11 has been linked to the malignant phenotype of clear cell renal cell carcinoma (ccRCC) promoting tumor growth, migration, and invasion [43]. SLFN11 is highly overexpressed in ccRCC where it is associated with poor overall survival [44]. Wang et al demonstrated that SLFN11 promotes the PI3K/AKT pathway supporting the increase of cellular proliferation, migration, and invasion as compared to ccRCC cells that lack SLFN11.…”