A multidimensional pan‐cancer analysis of DCAF13 and its protumorigenic effect in lung adenocarcinoma. Issue 4 (8th March 2023)

• Record Type: Journal Article
• Authors: Wei, Shan; Lu, Kaining; Xing, Jing; Yu, Wanjun
• Is Part Of: FASEB journal. Volume 37:Issue 4(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-03-08
• Subjects: DCAF13 -- immune checkpoint -- immunosuppressive microenvironment -- pan‐cancer -- prognosis; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.202201022RRR
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract: DCAF13 is a substrate recognition protein in the ubiquitin‐proteasome system with oncogenic effects in several malignant tumors. However, it is unclear that the relationship between DCAF13 expression pattern and prognosis across different cancer types. Also unknown is the biological function or effects on the immune microenvironment of DCAF13. In this study, we parsed multiple public databases to explore the potential tumorigenic actions of DCAF13, including correlations with prognosis, microsatellite instability (MSI), tumor mutational burden (TMB), immune checkpoint genes, immune cell infiltration, and immunotherapy response in pan‐cancer. Moreover, we validated DCAF13 expression in a tissue microarray by immunohistochemistry and investigate its effects in vitro and in vivo. The results showed that DCAF13 was upregulated in 17 cancer types and correlated with poor prognosis in many cancers. Also, the correlation between DCAF13 and TMB was found in 14 cancers as well as MSI in nine. The expression level of DCAF13 was found to be notably correlated with immune cell infiltration, showing a negative correlation with CD4 T cell infiltration and a positive correlation with neutrophil infiltration. The oncogene DCAF13 expression was shown to have a positive correlation with CD274 or ADORA2A and negative correlation with VSIR, TNFRSF4, or TNFRSF14 across large subsets of human cancers. Finally, we observed that DCAF13 was highly expressed in a tissue microarray of lung cancer. In immunocompromised mouse models, xenograft growth of human lung cancer cells was significantly inhibited by DCAF13 knockdown. Our results highlighted the value of DCAF13 as a promising independent predictor of poor prognosis through numerous biological processes. High DCAF13 expression often predicts suppressive immune microenvironment and immunotherapy resistance in a pan‐cancer context. Abstract : DCAF13 is highly expressed and correlates with poor prognosis or TMB or MSI in many cancers. High DCAF13 expression predicts an immunosuppressive microenvironment, including decreased CD4 T cell infiltration and increased neutrophil infiltration. The DCAF13 expression positively correlates with CD274 or ADORA2A and negatively correlates with VSIR, TNFRSF4, or TNFRSF14. Finally, we demonstrate that DCAF13 expression is elevated in LUAD tissue microarrays, as well as promoting DTX3 mRNA expression to contribute to LUAD cell proliferation in vitro and in vivo.