Proteomics of Primary Uveal Melanoma: Insights into Metastasis and Protein Biomarkers

Jang, Geeng-Fu; Crabb, John S.; Hu, Bo; Willard, Belinda; Kalirai, Helen; Singh, Arun D.; Coupland, Sarah E.; Crabb, John W.

doi:10.3390/cancers13143520

Cited by 11 publications

(18 citation statements)

References 76 publications

(115 reference statements)

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“…Comprehensive proteomic analysis has started to contribute to better define the prognosis of UM patients. The largest study involving proteomic analysis of primary UM patients using a LC MS/MS iTRAQ methodology was unveiled recently, involving 53 metastasizing and 47 non-metastasizing cases [ 291 ]. In all studied cases, nearly 3935 different proteins were evaluated and bioinformatics analyses allowed the identification of 191 differentially expressed proteins elevated in metastatic cases and 211 differentially expressed proteins elevated in non-metastatic cases [ 291 ].…”

Section: Additional Novel Promising Molecular Biomarkers In Uveal Melanoma With Prognostic Relevancementioning

confidence: 99%

“…The largest study involving proteomic analysis of primary UM patients using a LC MS/MS iTRAQ methodology was unveiled recently, involving 53 metastasizing and 47 non-metastasizing cases [ 291 ]. In all studied cases, nearly 3935 different proteins were evaluated and bioinformatics analyses allowed the identification of 191 differentially expressed proteins elevated in metastatic cases and 211 differentially expressed proteins elevated in non-metastatic cases [ 291 ]. Reactome pathway analysis of proteins preferentially elevated in metastatic UM showed mostly an overrepresentation of immune system pathways, but also pathways associated with vesicle-mediated trafficking, extracellular matrix organization, metabolism of proteins and homeostasis [ 291 ].…”

Section: Additional Novel Promising Molecular Biomarkers In Uveal Melanoma With Prognostic Relevancementioning

confidence: 99%

“…In all studied cases, nearly 3935 different proteins were evaluated and bioinformatics analyses allowed the identification of 191 differentially expressed proteins elevated in metastatic cases and 211 differentially expressed proteins elevated in non-metastatic cases [ 291 ]. Reactome pathway analysis of proteins preferentially elevated in metastatic UM showed mostly an overrepresentation of immune system pathways, but also pathways associated with vesicle-mediated trafficking, extracellular matrix organization, metabolism of proteins and homeostasis [ 291 ]. On the other hand, in non-metastatic cases, the authors demonstrated a preponderance of pathways connected with metabolism, but also cellular response to external stimuli and developmental biology [ 291 ].…”

Section: Additional Novel Promising Molecular Biomarkers In Uveal Melanoma With Prognostic Relevancementioning

confidence: 99%

“…Reactome pathway analysis of proteins preferentially elevated in metastatic UM showed mostly an overrepresentation of immune system pathways, but also pathways associated with vesicle-mediated trafficking, extracellular matrix organization, metabolism of proteins and homeostasis [ 291 ]. On the other hand, in non-metastatic cases, the authors demonstrated a preponderance of pathways connected with metabolism, but also cellular response to external stimuli and developmental biology [ 291 ]. Interestingly, the over-representation of proteins of the immune system pathways was more relevant in metastatic cases, while housekeeping pathways were over-represented in non-metastatic cases [ 291 ].…”

Section: Additional Novel Promising Molecular Biomarkers In Uveal Melanoma With Prognostic Relevancementioning

confidence: 99%

“…On the other hand, in non-metastatic cases, the authors demonstrated a preponderance of pathways connected with metabolism, but also cellular response to external stimuli and developmental biology [ 291 ]. Interestingly, the over-representation of proteins of the immune system pathways was more relevant in metastatic cases, while housekeeping pathways were over-represented in non-metastatic cases [ 291 ]. This study helped to highlight the immune suppressive nature in primary UM, demonstrating a rather low abundance of immune checkpoint regulator molecules [ 291 ].…”

Section: Additional Novel Promising Molecular Biomarkers In Uveal Melanoma With Prognostic Relevancementioning

confidence: 99%

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Prognostic Biomarkers in Uveal Melanoma: The Status Quo, Recent Advances and Future Directions

Lamas

Martel

Nahon-Estève

et al. 2021

Cancers

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Uveal melanoma (UM) is the most common malignant intraocular tumour in the adult population. It is a rare cancer with an incidence of nearly five cases per million inhabitants per year, which develops from the uncontrolled proliferation of melanocytes in the choroid (≈90%), ciliary body (≈6%) or iris (≈4%). Patients initially present either with symptoms like blurred vision or photopsia, or without symptoms, with the tumour being detected in routine eye exams. Over the course of the disease, metastases, which are initially dormant, develop in nearly 50% of patients, preferentially in the liver. Despite decades of intensive research, the only approach proven to mildly control disease spread are early treatments directed to ablate liver metastases, such as surgical excision or chemoembolization. However, most patients have a limited life expectancy once metastases are detected, since there are limited therapeutic approaches for the metastatic disease, including immunotherapy, which unlike in cutaneous melanoma, has been mostly ineffective for UM patients. Therefore, in order to offer the best care possible to these patients, there is an urgent need to find robust models that can accurately predict the prognosis of UM, as well as therapeutic strategies that effectively block and/or limit the spread of the metastatic disease. Here, we initially summarized the current knowledge about UM by compiling the most relevant epidemiological, clinical, pathological and molecular data. Then, we revisited the most important prognostic factors currently used for the evaluation and follow-up of primary UM cases. Afterwards, we addressed emerging prognostic biomarkers in UM, by comprehensively reviewing gene signatures, immunohistochemistry-based markers and proteomic markers resulting from research studies conducted over the past three years. Finally, we discussed the current hurdles in the field and anticipated the future challenges and novel avenues of research in UM.

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Section: Additional Novel Promising Molecular Biomarkers In Uveal Melanoma With Prognostic Relevancementioning

confidence: 99%

Section: Additional Novel Promising Molecular Biomarkers In Uveal Melanoma With Prognostic Relevancementioning

confidence: 99%

Section: Additional Novel Promising Molecular Biomarkers In Uveal Melanoma With Prognostic Relevancementioning

confidence: 99%

Section: Additional Novel Promising Molecular Biomarkers In Uveal Melanoma With Prognostic Relevancementioning

confidence: 99%

Section: Additional Novel Promising Molecular Biomarkers In Uveal Melanoma With Prognostic Relevancementioning

confidence: 99%

See 3 more Smart Citations

Prognostic Biomarkers in Uveal Melanoma: The Status Quo, Recent Advances and Future Directions

Lamas

Martel

Nahon-Estève

et al. 2021

Cancers

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Programmed Cell Death-Related Gene Signature Associated with Prognosis and Immune Infiltration and the Roles of HMOX1 in the Proliferation and Apoptosis were Investigated in Uveal Melanoma

Zhao,

Wang,

et al. 2024

Genes Genom

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Background Uveal melanoma (UVM) is the most common primary ocular malignancy, with a wide range of symptoms and outcomes. The programmed cell death (PCD) plays an important role in tumor development, diagnosis, and prognosis. There is still no research on the relationship between PCD-related genes and UVM. A novel PCD-associated prognostic model is urgently needed to improve treatment strategies. Objective We aim to screen PCD-related prognostic signature and investigate its proliferation ability and apoptosis in UVM cells. Methods The clinical information and RNA-seq data of the UVM patients were collected from the TCGA cohort. All the patients were classified using consensus clustering by the selected PCD-related genes. After univariate Cox regression and PPI network analysis, the prognostic PCD-related genes were then submitted to the LASSO regression analysis to build a prognostic model. The level of immune infiltration of 8-PCD signature in high- and low-risk patients was analyzed using xCell. The prediction on chemotherapy and immunotherapy response in UVM patients was assessed by GDSC and TIDE algorithm. CCK-8, western blot and Annexin V-FITC/PI staining were used to explore the roles of HMOX1 in UVM cells. Results A total of 8-PCD signature was constructed and the risk score of the PCD signature was negatively correlated with the overall survival, indicating strong predictive ability and independent prognostic value. The risk score was positively correlated with CD8 Tcm, CD8 Tem and Th2 cells. Immune cells in high-risk group had poorer overall survival. The drug sensitivity demonstrated that cisplatin might impact the progression of UVM and better immunotherapy responsiveness in the high-risk group. Finally, Overespression HMOX1 (OE-HMOX1) decreased the cell viability and induced apoptosis in UVM cells. Recuse experiment results showed that ferrostatin-1 (fer-1) protected MP65 cells from apoptosis and necrosis caused by OE-HMOX1. Conclusion The PCD signature may have a significant role in the tumor microenvironment, clinicopathological characteristics, prognosis and drug sensitivity. More importantly, HMOX1 depletion greatly induced tumor cell growth and inhibited cell apoptosis and fer-1 protected UVM cells from apoptosis and necrosis induced by OE-HMOX1. This work provides a foundation for effective therapeutic strategy in tumour treatment.

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Protein Kinase Signaling Networks Driven by Oncogenic Gq/11 in Uveal Melanoma Identified by Phosphoproteomic and Bioinformatic Analyses

Onken,

Erdmann-Gilmore,

Zhang

et al. 2023

Molecular & Cellular Proteomics

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Proteomics of Primary Uveal Melanoma: Insights into Metastasis and Protein Biomarkers

Cited by 11 publications

References 76 publications

Prognostic Biomarkers in Uveal Melanoma: The Status Quo, Recent Advances and Future Directions

Prognostic Biomarkers in Uveal Melanoma: The Status Quo, Recent Advances and Future Directions

Programmed Cell Death-Related Gene Signature Associated with Prognosis and Immune Infiltration and the Roles of HMOX1 in the Proliferation and Apoptosis were Investigated in Uveal Melanoma

Protein Kinase Signaling Networks Driven by Oncogenic Gq/11 in Uveal Melanoma Identified by Phosphoproteomic and Bioinformatic Analyses

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