Thyrotroph embryonic factor is downregulated in bladder cancer and suppresses proliferation and tumorigenesis via the AKT/FOXOs signalling pathway

304 Background: Bladder cancer is the 7th cause of death from cancer in men and 10th in women. For metastatic patients, prognosis is poor with a median overall survival of 15 months that remained unchanged for the past 15 years. No standard second-line chemotherapy is available for patients who relapse. Acquired mutations leading to a deregulation of the PI3K/AKT/mTOR pathway have been reported in more than 40% of bladder cancers suggesting the use of the mTOR (mammalian target of rapamycin) signalling pathway as an attractive target for the treatment of urothelial tumors. Methods: The main objective of this study was to assess the efficacy of temsirolimus, an mTOR inhibitor that is already used for the treatment of renal cancers, in patients with recurrent or metastatic bladder cancer who already received a first line chemotherapy. Efficacy was measured in terms of non-progression of the disease at two months of treatment following the RECIST v1.1 criteria. Based on a two-stage optimal Simon’s design, a total of 15 non-progressions out of 51 eligible and assessable patients were required to claim efficacy. Patients were treated at a weekly dose of 25 mg until progression, unacceptable toxicities or withdrawal. Results: Fifty-four patients were enrolled in the study between November 2009 and July 2014 in seven French centres. At the end of the first stage, six patients out of 17 were progression-free at 2 months leading to the inclusion of additional 37 patients in the second stage of the study. Thirty-six patients were eligible and assessable for the primary efficacy endpoint. A total of 18 (50%) non-progressions were observed at 2 months. Among them, partial response was documented for two patients and stable disease for 16. Twenty-five related adverse events were observed in 19 (35.2%) of the patients. Conclusions: Our study is providing the first clinical evidence of a potential benefit of temsirolimus for the treatment of relapsed bladder cancers. Ancillary study is ongoing to investigate the mutational status of genes which are involved in the PI3K/AKT/mTOR signalling pathway in order to identify a predictive signature of response to temsirolimus in bladder cancer. Clinical trial information: NCT0187943NCT0187943.

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Long non-coding RNA SNHG20 promotes bladder cancer via activating the Wnt/β-catenin signalling pathway

International Journal of Molecular Medicine ◽

10.3892/ijmm.2018.3819 ◽

2018 ◽

Cited By ~ 2

Author(s):

Qingsong Zhao ◽

Saiyue Gao ◽

Qingyan Du ◽

Ye Liu

Keyword(s):

Bladder Cancer ◽

Signalling Pathway ◽

Non Coding Rna ◽

Long Non Coding Rna

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Wnt signalling pathway in bladder cancer

Cellular Signalling ◽

10.1016/j.cellsig.2020.109886 ◽

2021 ◽

Vol 79 ◽

pp. 109886

Author(s):

Guanlin Wu ◽

Weidong Weng ◽

Pengfei Xia ◽

Shixian Yan ◽

Cheng Zhong ◽

...

Keyword(s):

Bladder Cancer ◽

Wnt Signalling ◽

Signalling Pathway ◽

Wnt Signalling Pathway

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Long non-coding RNA LINC02446 suppresses the proliferation and metastasis of bladder cancer cells by binding with EIF3G and regulating the mTOR signalling pathway

Cancer Gene Therapy ◽

10.1038/s41417-020-00285-2 ◽

2021 ◽

Author(s):

Xiaotong Zhang ◽

Jiarun Zhang ◽

Wei Zhao ◽

Xiao Dong ◽

Peng Xin ◽

...

Keyword(s):

Bladder Cancer ◽

Cancer Cells ◽

Signalling Pathway ◽

Non Coding Rna ◽

Bladder Cancer Cells ◽

Proliferation And Metastasis ◽

Long Non Coding Rna ◽

Mtor Signalling ◽

Mtor Signalling Pathway

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Identification of Hub Genes related to the Progression of Bladder Cancer by an Integrated Bioinformatics Analysis

10.21203/rs.3.rs-819606/v1 ◽

2021 ◽

Author(s):

Han Wang ◽

Jieqing Chen ◽

Xinhui Liao ◽

Yang Liu ◽

Aifa Tang ◽

...

Keyword(s):

Bladder Cancer ◽

Differentially Expressed Genes ◽

Molecular Mechanisms ◽

Signalling Pathway ◽

Gene Set Enrichment Analysis ◽

Differentially Expressed ◽

Hub Genes ◽

Immune Infiltration ◽

Ppi Networks ◽

Normal Bladder

Abstract BACKGROUND and OBJECTIVE: A better understanding of the molecular mechanisms underlying bladder cancer is necessary to identify candidate therapeutic targets. METHODS: We screened for genes associated with bladder cancer progression and prognosis. Publicly available expression data were obtained from TCGA and GEO to identify differentially expressed genes (DEGs) between bladder cancer and normal bladder tissues. Weighted co-expression networks were constructed, and Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Associations between hub genes and immune infiltration and immune therapy were evaluated. RESULTS: 3461 DEGs in TCGA-BC and 1069 DEGs in the GSE dataset were identified, with 87 overlapping differentially expressed genes between the bladder cancer and normal bladder groups. Hub genes in the tumour group were mainly enriched for cell proliferation-related GO terms and KEGG pathways, while hub genes in the normal group were related to the synthesis and secretion of neurotransmitters. PPI networks for the genes identified in the normal and tumour groups were constructed. Based on a survival analysis, CDH19, RELN, PLP1, and TRIB3 were significantly associated with prognosis (P < 0.05). Four hub genes were significantly enriched in the MAPK signalling pathway, VEGF signalling pathway, WNT signalling pathway, cell cycle, and P53 signalling pathway based on a gene set enrichment analysis; these genes were associated with immune infiltration levels in bladder cancer. CONCLUSIONS: CDH19, RELN, PLP1, and TRIB3 may play important roles in the development of bladder cancer and are potential therapeutic and prognostic targets.

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