Differential Expression of Fourteen Proteins between Uveal Melanoma from Patients Who Subsequently Developed Distant Metastases versus Those Who Did Not

Linge, Annett; Kennedy, Susan; O'Flynn, Deirdre; Beatty, Stephen; Moriarty, Paul; Henry, Michael; Clynes, Martin; Larkin, Annemarie; Meleady, Paula

doi:10.1167/iovs.11-9019

Cited by 56 publications

(54 citation statements)

References 46 publications

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“…This is in accordance with our finding that peptides of TUBB (m/z: 1618) were identified as being upregulated in ccRCC patients. TUBB was also reported to be associated with other cancers, and could decrease expression in uveal melanomas that subsequently metastasized compared with those that did not [36]. In cases of ovarian carcinoma, high expression levels of class III beta-tubulin appeared to be associated with earlier recurrence [37].…”

Section: Discussionmentioning

confidence: 97%

Identification of Potential Serum Proteomic Biomarkers for Clear Cell Renal Cell Carcinoma

Yang

Zhao

et al. 2014

PLoS ONE

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ObjectiveTo investigate discriminating protein patterns and serum biomarkers between clear cell renal cell carcinoma (ccRCC) patients and healthy controls, as well as between paired pre- and post-operative ccRCC patients.MethodsWe used magnetic bead-based separation followed by matrix-assisted laser desorption ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) to identify patients with ccRCC. A total of 162 serum samples were analyzed in this study, among which there were 58 serum samples from ccRCC patients, 40 from additional paired pre- and post-operative ccRCC patients (n = 20), and 64 from healthy volunteers as healthy controls. ClinProTools software identified several distinct markers between ccRCC patients and healthy controls, as well as between pre- and post-operative patients.ResultsPatients with ccRCC could be identified with a mean sensitivity of 88.38% and a mean specificity of 91.67%. Of 67 m/z peaks that differed among the ccRCC, healthy controls, pre- and post-operative ccRCC patients, 24 were significantly different (P<0.05). Three candidate peaks, which were upregulated in ccRCC group and showed a tendency to return to healthy control values after surgery, were identified as peptide regions of RNA-binding protein 6 (RBP6), tubulin beta chain (TUBB), and zinc finger protein 3 (ZFP3) with the m/z values of 1466.98, 1618.22, and 5905.23, respectively.ConclusionMB-MALDI-TOF-MS method could generate serum peptidome profiles of ccRCC, and provide a new approach to identify potential biomarkers for diagnosis as well as prognosis of this malignancy.

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Section: Discussionmentioning

confidence: 97%

Identification of Potential Serum Proteomic Biomarkers for Clear Cell Renal Cell Carcinoma

Yang

Zhao

et al. 2014

PLoS ONE

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“…Interestingly, 112 proteins (84%) of the previously-reported dataset [22] were also present within our cohort. We also compared our secreted protein dataset with proteins reported in two studies that examined differentially expressed proteins in UM tissue from patients who went on to develop metastases and those who did not [36, 37]. In the study by Linge et al eight of the 14 proteins reported as differentially expressed between primary UM that metastasised and those that did not, were found in our secreted protein dataset; PDIA3, VIM/HEXA, SELENBP1, ERP29, TPI1, PARK7, EIF2S1 and RPSA [36].…”

Section: Discussionmentioning

confidence: 99%

In-depth proteomic profiling of the uveal melanoma secretome

et al. 2016

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Uveal melanoma (UM), the most common primary intraocular tumour in adults, is characterised by a high frequency of metastases to the liver, typically with a fatal outcome. Proteins secreted from cancer cells (‘secretome’) are biologically important molecules thought to contribute to tumour progression. We examined the UM secretome by applying a label-free nanoLCMS/MS proteomic approach to profile proteins secreted into culture media by primary UM tumours with a high− (HR; n = 11) or low− (LR; n = 4) metastatic risk, compared to normal choroidal melanocytes (NCM) from unaffected post-mortem eyes. Across the three groups, 1843 proteins were identified at a 1% false discovery rate; 758 of these by at least 3 unique peptides, and quantified. The majority (539/758, 71%) of proteins were classified as secreted either by classical (144, 19%), non-classical (43, 6%) or exosomal (352, 46%) mechanisms. Bioinformatic analyzes showed that the secretome composition reflects biological differences and similarities of the samples. Ingenuity® pathway analysis of the secreted protein dataset identified abundant proteins involved in cell proliferation-, growth- and movement. Hepatic fibrosis/hepatic stellate cell activation and the mTORC1-S6K signalling axis were among the most differentially regulated biological processes in UM as compared with NCM. Further analysis of proteins upregulated ≥ 2 in HR-UM only, identified exosomal proteins involved in extracellular matrix remodelling and cancer cell migration/invasion; as well as classically secreted proteins, possibly representing novel biomarkers of metastatic disease. In conclusion, UM secretome analysis identifies novel proteins and pathways that may contribute to metastatic development at distant sites, particularly in the liver.

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“…Tissue specimens were processed using standard procedures for formalin fixation, and were embedded in paraffin as normally performed for routine clinical analysis (Table I) (15). Upon completion of the histopathological diagnosis, additional 10-µm-thick sections were placed on glass slides, and were compared with haematoxylin and eosin (H&E)-stained slides from the same block to identify histologically distinct (tumour-rich) tissue regions.…”

Section: Methodsmentioning

confidence: 99%

Quantitative label-free mass spectrometry analysis of formalin-fixed, paraffin-embedded tissue representing the invasive cutaneous malignant melanoma proteome

et al. 2016

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Understanding the events at a protein level that govern the progression from melanoma in situ to invasive melanoma are important areas of current research to be developed. Recent advances in the analysis of formalin-fixed, paraffin-embedded tissue by proteomics, particularly using the filter-aided sample preparation protocol, has opened up the possibility of studying vast archives of clinical material and associated medical records. In the present study, quantitative protein profiling was performed using tandem mass spectrometry, and the proteome differences between melanoma in situ and invasive melanoma were compared. Biological pathway analyses revealed several signalling pathways differing between melanoma in situ and invasive melanoma, including metabolic pathways and the phosphoinositide 3-kinase-Akt signalling pathway. Selected proteins of interest (14–3-3ε and fatty acid synthase) were subsequently investigated using immunohistochemical analysis of tissue microarrays. Identifying the key proteins that play significant roles in the establishment of a more invasive phenotype in melanoma may ultimately aid diagnosis and treatment decisions.

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Differential Expression of Fourteen Proteins between Uveal Melanoma from Patients Who Subsequently Developed Distant Metastases versus Those Who Did Not

Cited by 56 publications

References 46 publications

Identification of Potential Serum Proteomic Biomarkers for Clear Cell Renal Cell Carcinoma

Identification of Potential Serum Proteomic Biomarkers for Clear Cell Renal Cell Carcinoma

In-depth proteomic profiling of the uveal melanoma secretome

Quantitative label-free mass spectrometry analysis of formalin-fixed, paraffin-embedded tissue representing the invasive cutaneous malignant melanoma proteome

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