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

Author(s)

Rangel, Maristela P. ^[1] ; de Sa, Vanessa K. ^{[1, 2]} ; Prieto, Tabatha ^[1] ; Martins, Joo Roberto M. ^{[3, 4]} ; Olivieri, Eloisa R. ^[2] ; Carraro, Dirce ^[2] ; Takagaki, Teresa ^[5] ; Capelozzi, Vera Luiza ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Patol, Fac Med, Sao Paulo, SP - Brazil

^[2] AC Camargo Canc Ctr, Ctr Int Pesquisa CIPE, Lab Genom & Mol Biol, Sao Paulo, SP - Brazil

^[3] Univ Fed Sao Paulo, Dept Bioquim, Disciplina Biol Mol, Fac Med, Sao Paulo, SP - Brazil

^[4] Univ Fed Sao Paulo, Dept Med, LEMT, Disciplina Endocrinol & Metab, Escola Paulista Med, Sao Paulo, SP - Brazil

^[5] Univ Sao Paulo, Inst Coracao Incor, Div Pneumol, Fac Med, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: GLYCOCONJUGATE JOURNAL; v. 35, n. 2, p. 233-242, APR 2018.
• Web of Science Citations: 6

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 (beta risk 11.64; 1.27 to 15.90) and low risk of death (beta risk 0.11; 0.02-0.51). The combined approach suggest matrix (PGs) as biomarkers in lung cancer. (AU)

• FAPESP's process: 10/11005-5 - Hyaluronan detection and cytokine gene expression: predictive and prognostic impact as new lung cancer markers
• Grantee: Vera Luiza Capelozzi
• Support Opportunities: Regular Research Grants