High TNFSF13B expression as a predictor of poor prognosis in adrenocortical carcinoma

Abstract

Background: Adrenocortical carcinoma (ACC) is an extremely rare malignant tumor with poor prognosis.Existing treatment options have limited effects, and new therapeutic targets urgently need to be discovered. TNFSF13B has been reported to be associated with the prognosis of clear cell renal cell carcinoma, but it has not been studied in ACC.Methods: TNFSF13B expression was analyzed and compared between ACC tumors and normal tissues by using public datasets from TCGA and GTEx. Kaplan-Meier analysis was employed to evaluate survival, and Cox regression was employed to evaluate clinicopathologic features. The upstream and downstream regulatory mechanisms of TNFSF13B were also analyzed. GSEA was performed to explore the mechanisms of TNFSF13B in ACC. Finally, 14 ACC clinical samples were used to verify the relationships between TNFSF13B expression and disease-free survival (DFS) and overall survival (OS).Results: TNFSF13B expression was significantly higher in ACC tissues than in normal tissues. The prognosis of ACC patients with high TNFSF13B expression was worse than that of patients with low TNFSF13B expression. High TNFSF13B expression was strongly correlated with poor prognosis, and TNFSF13B was a prognostic factor. TNFSF13B expression is modified by upstream miRNAs, methylation and ubiquitination, and downstream, it interacts with other proteins. GSEA showed that regulation of cholesterol biosynthesis by SREBP and SREBF, downstream signaling events of the B cell receptor (BCR) and activation of gene expression by SREBF and SREBP were significantly enriched in the TNFSF13B highexpression phenotype. Clinical samples confirmed that TNFSF13B expression was significantly associated with DFS but not with OS.Conclusions: TNFSF13B may be a potential prognostic molecular marker of poor survival in ACC patients, offering a new therapeutic target.

HOOK1 Inhibits the Progression of Renal Cell Carcinoma via TGF‐β and TNFSF13B/VEGF‐A Axis

“…[ 9 ] However, TNFSF13B has also been reported to exert a pivotal role in several other diseases, including neoplasia, such as breast cancer, glioblastoma, melanoma, and adrenocortical carcinoma. [ 10 , 11 , 12 , 13 ] Moreover, TNFSF13B is reported to enriched in tumor with hyperplastic blood vessels, and regarded as a biomarker for the metastases. [ 14 , 15 ] These data reinforced that TNFSF13B may play a key role in the progression of renal cell carcinoma, as RCC is strongly vascularized.…”

Identifying endoplasmic reticulum stress-related genes as new diagnostic and prognostic biomarkers in clear cell renal cell carcinoma

“…As a B lymphocyte stimulator, it is important for the survival, proliferation, and differentiation of B cells ( 24 ). In addition, TNFSF13B effectively promotes the apoptosis of various tumor cells, such as human lymphoma cells (U937), prostate cancer cells (PC-3), colon cancer cells (HT-29), cervical cancer cells (HeLa), breast cancer cells (MCF-7), and embryonic kidney cells (A293) ( 25 ). Previous studies have confirmed that TNFSF13B can not only predict the prognosis of ccRCC patients, but is also an important mediator of information transmission between tumor cells and the tumor microenvironment, and is a potential therapeutic target ( 26 ).…”

“…A GSEA is used to evaluate the distribution trend of genes in a pre-defined gene set in a gene table ranked by the phenotype correlation to determine their contribution to the phenotype ( 23 ). We obtained the background gene sets of “c2.kegg.v7.4.symbols” and “c5.go.v7.4.symbols” from the MSigDB ( 24 ) database, and we used the “clusterprofiler” R package to perform the GSEA ( 25 ). In this analysis, P<0.05 was considered statistically significant.…”

Bioinformatic analysis identifying Endoplasmic Reticulum Stress-Related genes as a new diagnostic and prognostic indicator in clear cell Renal Cell Carcinoma

“…As an important B lymphocyte stimulator, it is important for the survival, proliferation and differentiation of B cells (22). In addition, TNFSF13B can effectively promote the apoptosis of various tumor cells, such as human lymphoma cells (U937), prostate cancer cells (PC-3), colon cancer cells (HT-29), cervical cancer cells (HeLa), breast cancer cells cells (MCF-7) and embryonic kidney cells (A293) (23).…”