scholarly journals CD40 is Positively Correlated with the Expression of Nucleophosmin in Cisplatin-Resistant Bladder Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Chenshuo Luo ◽  
Ting Lei ◽  
Man Zhao ◽  
Qian Meng ◽  
Man Zhang

Objective. To verify and evaluate the value of CD40 as a noninvasive biomarker of cisplatin-resistant bladder cancer, we studied the expression of CD40 and the correlation between nucleophosmin (NPM1) and CD40 in cisplatin-resistant bladder cancer. Methods. Three cisplatin-resistant bladder cancer cell lines (T24/0.8DDP, BIU87/0.3DDP, and PUMC-91/0.6DDP) were studied, and lentivirus was used to silence NPM1 expression. The expression of CD40 and NPM1 in three NPM1 silencing bladder cancer cell lines were detected by fluorescence microscopy and Western Blot. The effects and proteomic bioinformatics of NPM1 gene knockout on cisplatin-resistant bladder cancer cells were analyzed by liquid chromatography-mass spectrometry (LC-MS) and gene ontology analysis (GO analysis). Results. The NPM1 gene was successfully silenced in three drug-resistant bladder cancer cell lines by lentivirus infection. The knockdown efficiency was 70%. After NPM1 gene knockout, 492 differential proteins were detected by LC-MS, whose fold change was more than 1.5 p<0.05. A total of 57022 peptides, 54347 unique peptides, and 6686 protein groups were identified in all proteins of the tested cells (FDR < 0.01). Hierarchical clustering and principal component analysis showed that 264 functional proteins were downregulated and 228 functional proteins were upregulated in the gene silencing group compared with those of the negative controls. By GO analysis, the proteins affected by NPM1 cover a large number of proteins with biological functions, which may play an important role in the development of tumor in 492 differential proteins. The CD40 was the most significantly downregulated protein after NPM1 silencing, with a difference of 2.6-fold change in abundance. Conclusions. There is a positive correlation between CD40 protein and NPM1 protein in drug-resistant bladder cancer. Because NPM1 can reflect the characteristics of bladder cancer, CD40 may be a more sensitive marker for monitoring the prognosis of bladder cancer.

2015 ◽  
Vol 36 (4) ◽  
pp. 253-261 ◽  
Author(s):  
Yoshinori TAOKA ◽  
Kazumasa MATSUMOTO ◽  
Kazuya OHASHI ◽  
Satoru MINAMIDA ◽  
Masahiro HAGIWARA ◽  
...  

1993 ◽  
Vol 150 (4) ◽  
pp. 1293-1297 ◽  
Author(s):  
Barbara K. Chang ◽  
Yayun Liang ◽  
David W. Miller ◽  
Raymond J. Bergeron ◽  
Carl W. Porter ◽  
...  

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 480-480
Author(s):  
Anirban P Mitra ◽  
Andrea Kokorovic ◽  
Tanner Miest ◽  
Vikram M Narayan ◽  
Debasish Sundi ◽  
...  

480 Background: Members of the forkhead transcription factor (FOX) family are important mediators of embryonic development and are known to be altered in a variety of cancers. The functional role of FOXF1 in bladder tumorigenesis and progression has not been clearly characterized thus far. This study investigated the clinical implications of differential FOXF1 expression in bladder cancer, and potential mechanisms by which its alteration can lead to tumor metastasis. Methods: Whole genome expression profiling was performed on paired primary tumors and nodal metastases from a radical cystectomy discovery cohort using Illumina HT12 v3-4 BeadChip arrays to identify FOXF1 as a top differentially expressed gene. Prognostic role of differential FOXF1 expression was validated on two independent cystectomy cohorts. Differential FOXF1 expression was also evaluated in murine orthotopic xenografts. Small interfering RNA was used to knock down FOXF1 in RT112 and UC6 bladder cancer cell lines to develop an in vitro model for assessment of metastatic potential. Next-generation sequencing and hierarchical clustering analysis were used to identify differentially altered genes secondary to FOXF1 knockdown. 186 biologically curated pathways were interrogated with internal validation to elucidate the downstream biologic mechanisms of metastasis. Results: In the discovery cohort, FOXF1 was a top differentially expressed gene with 3.6-fold lower expression in nodal metastases than paired primary tumors (n = 33, p < 0.001). Multivariable analyses in two validation cohorts (total n = 128) indicated that FOXF1 underexpression was associated with worse cancer-specific (p = 0.046) and overall survival (p = 0.006). Murine orthotopic xenografts (n = 13) established from human bladder cancer cell lines (UC3, UC6, UC14) showed FOXF1 underexpression in metastatic deposits compared with primary tumors (p = 0.004). Hierarchical clustering identified 40 differentially expressed genes between FOXF1-knockdown bladder cancer cell lines and their corresponding controls. Biological pathway interrogation showed differential enrichment for genes associated with mitogen-activated protein kinase signaling, focal adhesion and other carcinogenic pathways in FOXF1-knockdown cells compared with controls (normalized enrichment score ≥ 1.3). Conclusions: We identify and characterize FOXF1 as a novel regulatory molecule that potentially drives bladder cancer metastasis. This may be modulated through alterations in intracellular signaling and cellular adhesion. FOXF1 may serve as a prognostic biomarker that can identify patients at impending risk for metastasis who may benefit from more aggressive management.


2002 ◽  
Vol 1 (1) ◽  
pp. 42
Author(s):  
Vijay Sangar ◽  
Richard Cowan ◽  
Steve Roberts ◽  
Geoff Margison ◽  
Jolyon Hendry ◽  
...  

Oncotarget ◽  
2017 ◽  
Vol 8 (25) ◽  
pp. 40289-40304 ◽  
Author(s):  
Yang Yang ◽  
Chuangang Li ◽  
Hong Li ◽  
Moli Wu ◽  
Changle Ren ◽  
...  

Urology ◽  
1999 ◽  
Vol 53 (6) ◽  
pp. 1252-1257 ◽  
Author(s):  
Edward Morcos ◽  
Olof T Jansson ◽  
Jan Adolfsson ◽  
Gunnar Kratz ◽  
N.Peter Wiklund

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