Identification of MDM2 as a prognostic and immunotherapeutic biomarker in a comprehensive pan-cancer analysis: A promising target for breast cancer, bladder cancer and ovarian cancer immunotherapy

Zheng, Jialiang; Miao, Fenglin; Zhao, Wei; Lin, Zong‐Hong; Chen, Yaqin; Kong, Xu; Wang, Yue; Zhuang, Aobo; Wu, Ting; Li, Wengang

doi:10.1016/j.lfs.2023.121832

Cited by 4 publications

(1 citation statement)

References 98 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, recent findings suggested that Fibronectin-1 levels may forecast the success of immunotherapy in MIBC, with higher expression levels correlating with an increase in immunosuppressive cell infiltration [ 40 ]. Additionally, MDM2 had been identified as a marker linked with the anti-tumor immune response, offering prognostic insights for bladder cancer [ 41 ]. The presence of circulating tumor cells (CTCs) in the bloodstream also served as an indicator of progression and a poor prognosis for NMIBC and metastatic bladder cancer patients [ 42 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

Gut microbiota Parabacteroides distasonis enchances the efficacy of immunotherapy for bladder cancer by activating anti-tumor immune responses

Wang,

Qiu,

Xie

et al. 2024

BMC Microbiol

View full text Add to dashboard Cite

Objective Bladder cancer(BCa) was a disease that seriously affects patients’ quality of life and prognosis. To address this issue, many researches suggested that the gut microbiota modulated tumor response to treatment; however, this had not been well-characterized in bladder cancer. In this study, our objective was to determine whether the diversity and composition of the gut microbiota or the density of specific bacterial genera influence the prognosis of patients with bladder cancer. Methods We collected fecal samples from a total of 50 bladder cancer patients and 22 matched non-cancer individuals for 16S rDNA sequencing to investigate the distribution of Parabacteroides in these two groups. Further we conducted follow-up with cancer patients to access the impact of different genera of microorganisms on patients survival. We conducted a Fecal Microbiota Transplantation (FMT) and mono-colonization experiment with Parabacteroides distasonis to explore its potential enhancement of the efficacy of anti-PD-1 immunotherapy in MB49 tumor-bearing mice. Immunohistochemistry, transcriptomics and molecular experiment analyses were employed to uncover the underlying mechanisms. Results The 16S rDNA showed that abundance of the genus Parabacteroides was elevated in the non-cancer control group compared to bladder cancer group. The results of tumor growth curves showed that a combination therapy of P. distasonis and ICIs treatment significantly delayed tumor growth and increased the intratumoral densities of both CD4+T and CD8+T cells. The results of transcriptome analysis demonstrated that the pathways associated with antitumoral immune response were remarkably upregulated in the P. distasonis gavage group. Conclusion P. distasonis delivery combined with α-PD-1 mAb could be a new strategy to enhance the effect of anti-PD-1 immunotherapy. This effect might be achieved by activating immune and antitumor related pathways.

show abstract

Section: Discussionmentioning

confidence: 99%

Gut microbiota Parabacteroides distasonis enchances the efficacy of immunotherapy for bladder cancer by activating anti-tumor immune responses

Wang,

Qiu,

Xie

et al. 2024

BMC Microbiol

View full text Add to dashboard Cite

show abstract

Discovery of ganoderic acid A (GAA) PROTACs as MDM2 protein degraders for the treatment of breast cancer

Li,

Zuo

et al. 2024

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

Expression of the checkpoint kinase BUB1 is a predictor of response to cancer therapies

Cicirò,

Ragusa,

Sala

2024

Sci Rep

View full text Add to dashboard Cite

The identification of clinically-relevant biomarkers is of upmost importance for the management of cancer, from diagnosis to treatment choices. We performed a pan-cancer analysis of the mitotic checkpoint budding uninhibited by benzimidazole 1 gene BUB1, in the attempt to ascertain its diagnostic and prognostic values, specifically in the context of drug response. BUB1 was found to be overexpressed in the majority of cancers, and particularly elevated in clinically aggressive molecular subtypes. Its expression was correlated with clinico-phenotypic features, notably tumour staging, size, invasion, hypoxia, and stemness. In terms of prognostic value, the expression of BUB1 bore differential clinical outcomes depending on the treatment administered in TCGA cancer cohorts, suggesting sensitivity or resistance, depending on the expression levels. We also integrated in vitro drug sensitivity data from public projects based on correlation between drug efficacy and BUB1 expression to produce a list of candidate compounds with differential responses according to BUB1 levels. Gene Ontology enrichment analyses revealed that BUB1 overexpression in cancer is associated with biological processes related to mitosis and chromosome segregation machinery, reflecting the mechanisms of action of drugs with a differential effect based on BUB1 expression.

show abstract

Identification of MDM2 as a prognostic and immunotherapeutic biomarker in a comprehensive pan-cancer analysis: A promising target for breast cancer, bladder cancer and ovarian cancer immunotherapy

Cited by 4 publications

References 98 publications

Gut microbiota Parabacteroides distasonis enchances the efficacy of immunotherapy for bladder cancer by activating anti-tumor immune responses

Gut microbiota Parabacteroides distasonis enchances the efficacy of immunotherapy for bladder cancer by activating anti-tumor immune responses

Discovery of ganoderic acid A (GAA) PROTACs as MDM2 protein degraders for the treatment of breast cancer

Expression of the checkpoint kinase BUB1 is a predictor of response to cancer therapies

Contact Info

Product

Resources

About