Inherited duplications of PPP2R3B predispose to nevi and melanoma via a C21orf91-driven proliferative phenotype

Polubothu, Satyamaanasa; Zecchin, Davide; Al-Olabi, Lara; Lionarons, Daniël A.; Harland, Mark; Horswell, Stuart; Thomas, Anna; Hunt, Lilian; Wlodarchak, Nathan; Aguilera, Paula; Brand, Sarah; Bryant, Dale; Carrera, Cristina; Chen, Hui; Elgar, Greg; Harwood, Catherine A.; Howell, Michael; Larue, Lionel; Loughlin, Sam; MacDonald, Jeffrey R.; Malvehy, Josep; Barberan, Sara Martin; Silva, Vanessa Martins da; Molina, Miriam; Morrogh, Deborah; Moulding, Dale; Nsengimana, Jérémie; Pittman, Alan; Puig‐Butillé, J.A.; Parmar, Kiran; Sebire, Neil J.; Scherer, Stephen W.; Stadnik, Paulina; Stanier, Philip; Tell, Gemma; Waelchli, Regula; Zarrei, Mehdi; Puig, Susana; Bataille, Véronique; Xing, Yongna; Healy, Eugene; Moore, Gudrun E.; Di, Wei-Li; Newton-Bishop, Julia; Downward, Julian; Kinsler, Veronica A.

doi:10.1038/s41436-021-01204-y

Cited by 6 publications

(2 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The expression of P4HB can regulate tumor development either collagen-dependently or collagen-independently 29 . PPP2R3B encodes PR70 and is widely expressed in cytoplasm, which is related to cancer development 30 . In tumor growth and apoptosis, programmed cell death (PDCD)5,a member of the programmed cell death protein family,plays an important role 31 .…”

Section: Discussionmentioning

confidence: 99%

Prognostic biomarkers for bladder cancer based on differentially expressed exosome-related genes

Shen,

Han,

Zhou

et al. 2023

Preprint

View full text Add to dashboard Cite

Background In cancer, exosomes play an important role in cell-to-cell communication, cancer metastasis,neovascularization, and drug resistance. Due to the lack of mechanistic studies regarding exosomes in bladder cancer (BCa), the goal of this study was to identify the significance of exosome-related genes in BCa.Methods Differentially expressed genes (DEGs) were analyzed using the Cancer Genome Atlas (TCGA) databases. DEGs closely associated with BCa patient survival were identified using Cox regression, least absolute shrinkage, and selection operator analyses. A prognostic model about exosomes was then developed and validated. To predict survival, a nomogram was developed.Results A prediction model was constructed using seventeen of the six hundred and fifty-six DEGs related to exosomes. A low-risk and high-risk group was then established for patients with BCa. Patients at high-risk group had a significantly worse prognosis than those at low-risk group. Further analysis showed a lower risk score was associated with higher expression of immune cell infiltration, including T cells regulatory (Tregs) and Mast cells activated, and immune checkpoint genes, including LGALS9 and TNFRSF14.Conclusions Using exosome-related genes, this study identified a novel biomarker that may be used to predict the outcome of BCa in the future.

show abstract

Section: Discussionmentioning

confidence: 99%

Prognostic biomarkers for bladder cancer based on differentially expressed exosome-related genes

Shen,

Han,

Zhou

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…The expression of P4HB can regulate tumor development either collagen-dependently or collagenindependently [29]. PPP2R3B encodes PR70 and is widely expressed in cytoplasm, which is related to cancer development [30]. In tumor growth and apoptosis, programmed cell death (PDCD5), a member of the programmed cell death protein family, plays an important role [31].…”

Section: Discussionmentioning

confidence: 99%

Development and validation of a exosome-related gene signature for predicting prognosis, immune infiltration and immunotherapeutic response in bladder cancer

Shen,

Han,

Zhou

et al. 2023

Preprint

View full text Add to dashboard Cite

Background Recent studies indicate exosomes play an important role in cell-to-cell communication, cancer metastasis, neovascularization, the regulation of the tumor immune microenvironment, and drug resistance in various tumors. However, the prognostic and therapeutic value of exosome-related genes in bladder cancer (BCa) remains to be determined. Hence, the goal of this study was to identify and validate a novel prognostic model based on exosome-associated genes for BCa patients Methods Differentially expressed exosome-related genes (DEGs) were analyzed using the Cancer Genome Atlas (TCGA) databases. DEGs closely associated with BCa patient survival prognosis were identified using Cox regression; and these genes are used for molecular typing. Moreover, we constructed a 17 multigene model using the least absolute shrinkage and selection operator (LASSO) Cox regression model. The five external cohorts (i.e., GSE13507, GSE32894, GSE31684, GSE48075, and IMvigor210) of BCa patients were used to validate the accuracy by KM plot, ROC and calibration curves. Subsequently, we assessed immune infiltration using seven published algorithms: TIMER, CIBERSORT, CIBERSORT-ABS, QUANTISEQ, MCPCOUNTER, XCELL, and EPIC. Furthermore, the correlation results between risk groups (scores) and overall survival, recognised immunoregolatory cells or common chemotherapeutic agents, clinicopathological data and immune checkpoint-related genes of BCa patients, were analyzed based on wilcox rank test, chi-square test, cox regression and spearman's correlation method. Additionally, we also preformed that the expression level of partial modeled genes was significantly associated with objective responses to anti-PD-1/PD-L1 treatment in the IMvigor210, GSE111636, GSE176307 or our Truce01 cohort. Results In BC patients, 156 exosome-related prognostic DEGs were identified, and were clustered into three classes. Subtypes C3 predicts worse OS, DSS, and PFS in patients with BCa. The prognostic model of 17 exosome-related genes showed good prediction performance by the TCGA training set, internal test set and five external verification sets. Our study also additionally confirmed that model riskscore was closely related with drug susceptibility, immune cell infiltration, and the prediction of immunotherapy efficacy. The high-risk group was characterized by a higher number of infiltrating macrophages M2 cells, and cancer-associated fibroblasts (CAFs). Lastly, we verified the protein and mRNA expression of six interested model-related genes (including AKR1B1, CGB5, CSPG4, P4HB, POLR3G and RAC3) from the Human Protein Atlas (HPA) and 10 paired BCa tissues collected by us. Conclusions In summary, the exosome-associated gene signature established by us exhibited a high predictive performance for the prognosis, immunotherapeutic responsiveness, and chemotherapeutic sensitivity of BCa. And, The model also might function as a chemotherapy and immune checkpoint inhibitor (ICI) treatment guidance.

show abstract

Congenital Naevi and Selected Naevoid Conditions

Kinsler,

Sebire

2024

Rook's Textbook of Dermatology

View full text Add to dashboard Cite

The understanding of congenital naevi has evolved rapidly in the last few years, with the discovery of many of the causative genes, and an increasing understanding of the phenotypic correlates of genotypic mosaicism in the skin. The classification of all congenital naevi is reviewed, based on phenotype, histology and genetics. This allows for the addition of new conditions as they are discovered, and for the regrouping of previously distinct disorders. The clinical features and extracutaneous associations of different congenital naevi are reviewed, as well as those of non‐naevus‐like developmental abnormalities of the skin.

show abstract

Inherited duplications of PPP2R3B predispose to nevi and melanoma via a C21orf91-driven proliferative phenotype

Cited by 6 publications

References 40 publications

Prognostic biomarkers for bladder cancer based on differentially expressed exosome-related genes

Prognostic biomarkers for bladder cancer based on differentially expressed exosome-related genes

Development and validation of a exosome-related gene signature for predicting prognosis, immune infiltration and immunotherapeutic response in bladder cancer

Congenital Naevi and Selected Naevoid Conditions

Contact Info

Product

Resources

About