Abstract 427: Impact of glycosaminoglycans on lung cancer diagnosis and prognosis of patients
Authors: Rangel Maristela P. , de Sá Vanessa K. , Martins João Roberto Maciel , Cuentas Edwin Roger P. , Mendes Aline , Carraro Dirce Maria , Olivieri Eloísa , Capelozzi Vera Luiza 
Published: July 2012

Introduction: Treatment of lung cancer patients depends on histological type, performance status and clinical stage. Because of limitations of these parameters in predicting disease behavior, different markers have been investigated to better discriminate lung cancer evolution. Glycosaminoglycans(GAGs) are important molecules of the extracellular matrix hydrating and maintaining the osmotic balance of tissues. Many have reported that GAGs have different behaviors when in the presence of malignant tissues. In this study, we sought to examine the sulfated GAGs and hyaluronan (HA) concentrations and their impact on diagnosis and/or prognosis of patients with non small cell lung cancer.

Methods: Sulfated GAGs and HA were examined in tumoral and non-tumoral tissues from 45 patients who underwent lobectomy for lung cancer. Their preoperative clinical stages were T1-3N0-1M0 and the mean follow-up was 19.3 months. Their histologic types were adenocarcinomas (n=23), squamous cells carcinomas (SqCC) (n=16) and large cell carcinoma (n=6). Tissue samples were dehydrated with acetone and incubated with a proteolytic enzyme. The HA chains were diluted (1:100) in blocking buffer [0.05M Tris-HCl, pH 7.4, 1% BSA]. The levels of HA were measured by a noncompetitive enzyme-linked immunosorbent assay (ELISA)-like fluorometric assay. The sulfated GAG chains (heparan, dermatan and chondroitin sulfate – HS, DS and CS), were precipitated with ethanol and the pellet was dried and dissolved in DNAse(5μl/mg).The different types of sulfated GAGs and their concentration were identified after gel electrophoresis in diaminopropane buffer.

Results: A distinct profile of sulfated GAGs and HA was observed between non-tumoral and tumoral areas. HS and HA showed significantly higher concentration in tumoral than in non-tumoral areas (p=0.02 and p=0.0001, respectively). The adenocarcinomas had higher amounts of HS than SqCC specimens(p=0.02). One hundred % of tumoral areas presented CS while the normal almost never (p&lt;0.0001). The impact of HA was tested on follow-up until death from surgery day. The Kaplan-Meier survival curve showed that tissues with lower concentrations of HA have better long-term survival than those with higher concentrations (Log Rank=3.59; p=0.05).

Conclusion: The presence of CS and higher concentrations of HS and HA in patients with lung cancer suggest a possible role of those molecules in this disease, but more importantly provide potential biochemical markers for differentiating normal from lung cancer patients. The correlation between the histologic types and the amounts of HS provide a possible role of this GAG on the development of tumor aggressiveness considering that one of its functions is to bind itself to growth factors and regulate their action. However, further studies are needed to determine whether or not these concentrations are able to be diagnostic/prognostic markers of lung cancer.

Financial support: FAPESP

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 427. doi:10.1158/1538-7445.AM2011-427