Dataset Information

HnRNP M and HSP 90α as Potential Biomarkers in Early Stage Cutaneous Head and Neck Melanoma Tissue

ABSTRACT: Background: Timely diagnosis is important for successful treatment of cutaneous melanoma. Currently, Breslow tumor thickness and mitotic rate are used for malignant melanoma classification and prognosis, but these parameters can assess disease progression risk only to a certain degree. Therefore, there is a need for new melanoma protein biomarkers that would aid early and accurate diagnosis and prediction of their metastatic potential. Methodology and Findings: This retrospective case control study is based on proteomic profiling of formalin-fixed archival tissues of 31 early-stage head and neck cutaneous malignant melanoma samples using liquid chromatography / mass spectrometry. A melanoma proteomic profile was identified and protein expression levels were compared to the proteome profile of melanocytic naevi and correlated to established prognostic factors and disease-specific survival. In accordance with the American Joint Committee on Cancer guidelines, recursive partitioning multivariate analysis was used to identify potential biomarkers associated with metastatic potential of early-melanoma. Heterogeneous nuclear ribonucleoprotein M and heat shock protein 90 alpha were profiled as independent prognostic factors. Their elevated expression was clinically relevant for predicting an exceedingly high metastatic hazard ratio. These proteins were superior in estimating disease progression risk when compared to Breslow thickness and mitotic rate. Conclusions and Significance: Identification of biomarkers in early stage cutaneous head and neck melanoma is an important step towards predicting metastatic potential and prognosis of the disease. Clinical confirmation and further validation of the proteins identified in this study would provide a novel tool for identifying patients at risk for developing metastatic disease.

INSTRUMENT(S): LTQ Orbitap Discovery

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Skin

DISEASE(S): Head And Neck Cancer

SUBMITTER: Ruđer Novak

LAB HEAD: Lovorka Grgurević

PROVIDER: PXD015137 | Pride | 2019-11-27

REPOSITORIES: Pride

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Publications

Tumor tissue hnRNP M and HSP 90α as potential predictors of disease-specific mortality in patients with early-stage cutaneous head and neck melanoma: A proteomics-based study.

Košec Andro A Novak Ruđer R Konjevoda Paško P Trkulja Vladimir V Bedeković Vladimir V Grgurević Lovorka L

Oncotarget 20191119 62

<h4>Background</h4>Breslow tumor thickness and mitotic rate are standardly used for risk stratification of patients with malignant melanoma. However, their prognostic value is relatively limited and a need for improved prognostication has been advocated. We aimed to screen the tumor tissue proteome in a search for potentially useful prognostic factors in early-stage cutaneous head and neck melanoma.<h4>Methodology and findings</h4>Proteomic profiles of archival formalin-fixed tissue samples of 3 ...[more]

PMID: 31803364

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Project description:The present study deals with functional interactions of cutaneous and brain-metastasizing human melanoma cells with brain-derived molecules. In this study we employed the unique melanoma xenograft model developed by Izraely and described in Int J Cancer. 2011 Oct 25. doi: 10.1002/ijc.27324. The present study aims to determine if brain-derived soluble factors regulate malignancy-associated functions of cutaneous and brain-metastasizing melanoma cells and identify which functions are regulated by such factors. The working hypothesis of this study is that the interactions between the brain microenvironment and melanoma cells determine metastasis formation at this organ site. The aim of the study was to evaluate the contribution of such interactions to the formation of brain metastasis in nude mice xenografted with human melanoma cells. An insight into these interactions is an essential pre-requisite for the development of effective targeted therapy for melanoma brain metastasis. We assessed the effects of soluble factors present in supernatants of short-term cultures of normal mouse brain (referred here after as brain-derived soluble factors) on several characteristics linked to melanoma brain metastasis. It was found that brain-derived soluble factors affect differentially cutaneous and brain-metastasizing melanoma cells variants in-vitro. Such factors enhanced the viability of cutaneous melanoma cells but caused an S phase arrest followed by apoptosis of brain-metastasizing cells. Brain-derived soluble factors enhanced migration of melanoma cells metastasizing to the brain, but did not affect the migration of the cutaneous variants. Such factors up-regulated the expression of the chemokine receptor CCR4 in both cutaneous and brain metastasizing melanoma cells. It is not unlikely that CCR4 ligands expressed in the brain interact with the CCR4-expressing melanoma cells thereby directing them to the brain. Brain-derived soluble factors enhanced the transmigration, across human brain endothelial cells of cutaneous but not of brain metastasizing melanoma variants. This activity could promote the capacity of the cutaneous cells to metastasize to the brain. 4 Samples (arrays) were analyzed. There is 1 replicate for each variant and each treatment. We generated pairwise comparisons between cutaneous and brain metastatic variants of the same genetic background, using Partek Genomics Suite, in the three melanoma models. Genes with p≤5% and a fold-change difference of ≥2 or <-2 were selected.

Dataset Information

HnRNP M and HSP 90α as Potential Biomarkers in Early Stage Cutaneous Head and Neck Melanoma Tissue

Publications

Tumor tissue hnRNP M and HSP 90α as potential predictors of disease-specific mortality in patients with early-stage cutaneous head and neck melanoma: A proteomics-based study.

Similar Datasets

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