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Glycoconj J. 2018 Apr;35(2):233-242. doi: 10.1007/s10719-018-9815-x. Epub 2018 Mar 3.

Biomolecular analysis of matrix proteoglycans as biomarkers in non small cell lung cancer.

Author information

1
Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
2
Laboratory of Genomics and Molecular Biology, Centro Internacional de Pesquisa/CIPE, AC Camargo Cancer Center, São Paulo, SP, Brazil.
3
Disciplina de Biologia Molecular, Departamento de Bioquímica, Faculdade de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
4
Disciplina de Endocrinologia e Metabolismo, Laboratório de Endocrinologia Molecular e Translacional-LEMT, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
5
Divisao de Pneumologia, Instituto do Coraçao (Incor), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
6
Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil. vera.capelozzi@fm.usp.br.

Abstract

Matrix proteoglycans (PGs) have shown promise as biomarker in malignancies. We employed agarose gel eletrophoresis, quantitative real- time reverse transcription-polymerase chain reaction and immunohistochemistry to evaluate the content of sulfated glicosaminoglycans (chondroitin sulfate and heparan sulfate) and expression of PG (biglycan, glypican, perlecan, syndecan e versican) in patient-matched normal and tumor tissues obtained from resected specimens of lung cancer. A significant increase of heparan sulfate (HS) and chondroitin sulfate (CS) concentrations was found in tumor tissue samples when compared to normal lung tissue samples. HS was also significantly increased in adenocarcinomas compared to squamous cell carcinomas. PG gene expression, with exception of syndecan, were significantly decreased in tumor tissue compared to normal lung, coinciding with significant decrease of PG protein levels in tumor cells and stroma compared to normal lung tissue (Kappa coefficient 0.41, 0.42 and 0,28, respectively). Women patients (p = 0.02), non smokers (p = 0.05), T stage (p = 0.009), N stage (p = 0.03) and adenocarcinoma (p = 0.05) were associated with improved overall survival (OS). Patients presenting tumors with low concentration of sulfated GAG and high PGs levels presented better OS compared to patients with high concentration of sulfated GAG and low expression of PGs. Cox regression model controlled by gender, tobacco history and histological type, showed that patients with high perlecan and versican expression in tumor presented respectively high probability of life (β risk 11.64; 1.27 to 15.90) and low risk of death (β risk 0.11; 0.02-0.51). The combined approach suggest matrix (PGs) as biomarkers in lung cancer.

KEYWORDS:

Diagnosis; Extracellular matrix; Immunohistochemistry; Lung cancer; Prognosis; Proteoglycans; Survival

PMID:
29502190
DOI:
10.1007/s10719-018-9815-x
[Indexed for MEDLINE]

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