Dataset Information

Protein Oxidative Damage in UV-Related Skin Cancer and Dysplastic Lesions Contributes to Neoplastic Promotion and Progression.

ABSTRACT: The ultraviolet (UV) component of solar radiation is the major driving force of skin carcinogenesis. Most of studies on UV carcinogenesis actually focus on DNA damage while their proteome-damaging ability and its contribution to skin carcinogenesis have remained largely underexplored. A redox proteomic analysis of oxidized proteins in solar-induced neoplastic skin lesion and perilesional areas has been conducted showing that the protein oxidative burden mostly concerns a selected number of proteins participating to a defined set of functions, namely: chaperoning and stress response; protein folding/refolding and protein quality control; proteasomal function; DNA damage repair; protein- and vesicle-trafficking; cell architecture, adhesion/extra-cellular matrix (ECM) interaction; proliferation/oncosuppression; apoptosis/survival, all of them ultimately concurring either to structural damage repair or to damage detoxication and stress response. In peri-neoplastic areas the oxidative alterations are conducive to the persistence of genetic alterations, dysfunctional apoptosis surveillance, and a disrupted extracellular environment, thus creating the condition for transformant clones to establish, expand and progress. A comparatively lower burden of oxidative damage is observed in neoplastic areas. Such a finding can reflect an adaptive selection of best fitting clones to the sharply pro-oxidant neoplastic environment. In this context the DNA damage response appears severely perturbed, thus sustaining an increased genomic instability and an accelerated rate of neoplastic evolution. In conclusion UV radiation, in addition to being a cancer-initiating agent, can act, through protein oxidation, as a cancer-promoting agent and as an inducer of genomic instability concurring with the neoplastic progression of established lesions.

SUBMITTER: Tramutola A

PROVIDER: S-EPMC7017152 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

Protein Oxidative Damage in UV-Related Skin Cancer and Dysplastic Lesions Contributes to Neoplastic Promotion and Progression.

Tramutola Antonella A Falcucci Susanna S Brocco Umberto U Triani Francesca F Lanzillotta Chiara C Donati Michele M Panetta Chiara C Luzi Fabiola F Iavarone Federica F Vincenzoni Federica F Castagnola Massimo M Perluigi Marzia M Di Domenico Fabio F Marco Federico De F

Cancers 20200101 1

The ultraviolet (UV) component of solar radiation is the major driving force of skin carcinogenesis. Most of studies on UV carcinogenesis actually focus on DNA damage while their proteome-damaging ability and its contribution to skin carcinogenesis have remained largely underexplored. A redox proteomic analysis of oxidized proteins in solar-induced neoplastic skin lesion and perilesional areas has been conducted showing that the protein oxidative burden mostly concerns a selected number of prote ...[more]

PMID: 31906275

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Project description:The high prevalence of oral potentially-malignant disorders exhibits diverse severity and risk of malignant transformation, which mandates a Point-of-Care diagnostic tool. Low patient compliance for biopsies underscores the need for minimally-invasive diagnosis. Oral cytology, an apt method, is not clinically applicable due to a lack of definitive diagnostic criteria and subjective interpretation. The primary objective of this study was to identify and evaluate the efficacy of biomarkers for cytology-based delineation of high-risk oral lesions. A comprehensive systematic review and meta-analysis of biomarkers recognized a panel of markers (n: 10) delineating dysplastic oral lesions. In this observational cross sectional study, immunohistochemical validation (n: 131) identified a four-marker panel, CD44, Cyclin D1, SNA-1, and MAA, with the best sensitivity (>75%; AUC>0.75) in delineating benign, hyperplasia, and mild-dysplasia (Low Risk Lesions; LRL) from moderate-severe dysplasia (High Grade Dysplasia: HGD) along with cancer. Independent validation by cytology (n: 133) showed that expression of SNA-1 and CD44 significantly delineate HGD and cancer with high sensitivity (>83%). Multiplex validation in another cohort (n: 138), integrated with a machine learning model incorporating clinical parameters, further improved the sensitivity and specificity (>88%). Additionally, image automation with SNA-1 profiled data set also provided a high sensitivity (sensitivity: 86%). In the present study, cytology with a two-marker panel, detecting aberrant glycosylation and a glycoprotein, provided efficient risk stratification of oral lesions. Our study indicated that use of a two-biomarker panel (CD44/SNA-1) integrated with clinical parameters or SNA-1 with automated image analysis (Sensitivity >85%) or multiplexed two-marker panel analysis (Sensitivity: >90%) provided efficient risk stratification of oral lesions, indicating the significance of biomarker-integrated cytopathology in the development of a Point-of-care assay.

Dataset Information

Protein Oxidative Damage in UV-Related Skin Cancer and Dysplastic Lesions Contributes to Neoplastic Promotion and Progression.

Publications

Protein Oxidative Damage in UV-Related Skin Cancer and Dysplastic Lesions Contributes to Neoplastic Promotion and Progression.

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