DDX39 as a predictor of clinical prognosis and immune checkpoint therapy efficacy in patients with clear cell renal cell carcinoma

Abstract

DEAD-box protein 39 (DDX39) has been demonstrated to be a tumorigenic gene in multiple tumor types, but its role in the progression and immune microenvironment of clear cell renal cell cancer (ccRCC) remains unclear. The aim of the present study was to investigate the role of DDX39 in the ccRCC tumor progression, immune microenvironment and efficacy of immune checkpoint therapy. The DDX39 expression level was first detected in tumors in the public data and then verified in ccRCC samples from Changzheng Hospital. The prognostic value of DDX39 expression was assessed in the Cancer Genome Atlas (TCGA) and ccRCC patients from Changhai Hospital. The role of DDX39 in promoting ccRCC was analyzed by bioinformatic analysis and in vitro experiments. The association between DDX39 expression and immune cell infiltration and immune inhibitory markers was analyzed, and its value in predicting the immune checkpoint therapy efficacy in ccRCC were evaluated in the public database. DDX39 expression was elevated in Oncomine, GEO and TCGA ccRCC databases, as well as in Changzheng ccRCC samples. In TCGA ccRCC patients, increased DDX39 expression predicted worse overall survival (OS) ( p <0.0001) and progression-free interval (PFI) ( p <0.0001), and was shown as an independent predictive factor for OS ( p =0.002). These findings were consistent with those from Changhai ccRCC patients. In addition, GO and GSEA analysis identified DDX39 as a pro-ccRCC gene. In vitro experiments confirmed the role of DDX39 in promoting ccRCC cell. Finally, DDX39 was found to be positively correlated with a variety of immune inhibitory markers, and could predict the adverse efficacy of immune checkpoint therapy in TIDE analysis. In conclusion, Increased DDX39 in ccRCC patients predicted worse clinical prognosis, promoted ccRCC cell proliferation, migration and invasion, and also predicted adverse efficacy of immune checkpoint therapy.

LGALS1 was related to the prognosis of clear cell renal cell carcinoma identified by weighted correlation gene network analysis combined with differential gene expression analysis

“…Radical nephrectomy is the standard treatment for localized primary kidney cancer, but approximately one-quarter of these have relapses in distant sites ( Choueiri and Motzer 2017 ). With the development of bioinformatics, although some biomarkers related to ccRCC have been found in recent years, such as AOX1 ( Xiong et al, 2021 ), circCHST15 ( Gui et al, 2021 ), DDX39 ( Bao et al, 2021 ) and PPAR α ( Luo et al, 2019 ), the risk of death in patients with ccRCC is still high, so it is necessary to find more reliable markers and obtain more treatments to reduce the risk of death in patients with ccRCC. We identified 397 differentially expressed genes with consistent expression trends in the GSE46699 and TCGA-KIRC databases by WGCNA and Differential gene expression analysis.…”

A Prediction Model Using Alternative Splicing Events and the Immune Microenvironment Signature in Lung Adenocarcinoma

“…Overexpression of DDX39B predicts poor prognosis and promotes aggressiveness of melanoma ( 32 ). DDX39B can also predict adverse efficacy of immune checkpoint therapy in clear cell carcinoma ( 33 ). DDX39B serves as a potential drug target for the treatment of androgen receptor splice variant-positive prostate cancer ( 34 ).…”

Identification and Verification of m7G Modification Patterns and Characterization of Tumor Microenvironment Infiltration via Multi-Omics Analysis in Clear Cell Renal Cell Carcinoma

“…Immunohistochemical (IHC) staining was performed with EIF4A1 antibody (ab31217, Abcam) following the previous protocol ( 23 ). The IHC scores were calculated by staining intensity and the percentage of stained cells as reported ( 24 ).…”