Clinical relevance of matrix proteoglycans as predictors of lung cancer patients outcome

Author(s)

Maristela Peres Rangel

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD)
• Defense date: 2016-12-12

Examining board members

Vera Luiza Capelozzi; Ruy Gastaldoni Jaeger; Chin Jia Lin; Patricia Rieken Macedo Rocco; Lisete Ribeiro Teixeira

• Advisor: Vera Luiza Capelozzi

Abstract

Introduction. The relationship between the extracellular matrix (ECM) components and cancer cells have an important role on cancer development and progression. Between the most important molecules present on the ECM are the glycosaminoglycans and their respective proteoglycans. Studies have reported that they have different behaviours when in the presence of malignant tissues and influence the development of breast, pancreas and colon cancers. Likewise, proteins as solCD44 and cofilin-1 also have shown direct influence in tumor progression. Regarding that, there is growing interest among scientists in analyzing the expression of these molecules in body fluids as a screening tool of high risk patients and as a diagnostic and prognostic lung cancer biomarker. Objectives. The aims of this study were to recognize the impact of hyaluronan and the proteoglycans (biglycan, glypican, perlecan, syndecan e versican) on lung cancer carcinogenesis as well as its impact on patient\'s survival; verify if the solCD44 e cofilina-1 concentrations in the sputum of lung cancer patients could distinguish them from patients with COPD and healthy volunteers. Results. A direct association was found between tumors expressing high amounts of hyaluronan and CD34 in tumoral stroma. Heparan and chondroitin sulphate concentrations were higher in tumor specimens when compared to normal lung tissue. All proteoglycans, in exception of syndecan, showed a lower expression in tumoral tissue and biglycan and versican showed association with the clinical pathological features. Protein expression of biglycan, perlecan and versican was higher in the normal tissue when compared to stroma and tumoral cells. COX regression controlled by age, histological types and gene expression of biglycan, syndecan e glypican demonstrated that female patients had higher survival rates with high gene expression of perlecan and the patients with T1 stage, lack of linfonode Maristela Peres Rangel Tese de doutorado - USP metastasis and gene expression of versican had lower risk of death. Cofilin-1 concentration was higher in the sputum of lung cancer patients when compared to a high risk group and healthy volunteers. Also, the solCD44 concentration was higher in the sputum of lung cancer patients when compared to a high risk group and healthy volunteers. ROC cruve analysis demonstrated that sputum cofilin-1 was capable to distinguish high risk patients from lung cancer patients with na area under the curve of 0.69 and with a cut off at 802.5 pg/mL the curve presented 60% de sensitivity and 54% specificity. Sputum solCD44 was also capable to distinguish high risk patients from lung cancer patients with na area under the curve of 0.67 and with a cut off at 65.8 pg/mL the curve presented 50% de sensitivity and 84% specificity. Conclusions. Hyaluronan expression showed a correlation with tumoral growth through angiogenesis processes. The biomolecular analysis demonstrated that matrix proteoglycans are potencial lung cancer prognostic biomarkers. Sputum analyses showed that solCD44 and cofilin-1 are potencial molecules in lung cancer detection (AU)

• FAPESP's process: 12/06216-2 - ROLE OF PROTEOGLYCANS AS PROGNOSTIC AND PREDICTIVE BIOMARKERS ON NON SMALL CELL LUNG CANCER AND ITS IMPACT IN THE PULMONARY CARCINOGENESIS
• Grantee: Maristela Peres Rangel
• Support Opportunities: Scholarships in Brazil - Doctorate