Abstract 2574: Biglycan, tumor endothelial secreting proteoglycan, as possible biomarker for lung cancer

Abstract

Abstract [Backgroud and Purpose]: Tumor endothelial cells (TECs) have been reported to have various abnormalities. For example, TECs demonstrate higher expression levels of several molecules (TEC markers) compared with normal endothelial cells (NECs). Recently we identified biglycan (Bgn) as one of TEC markers. Bgn has been reported to be associated with tumor progression in various cancers. In addition, we have found that Bgn secreted by TEC promoted intravasation of tumor cells and lung metastasis in vivo mouse tumors. Lung cancer, of which non-small-cell lung cancer (NSCLC) is the most common form, remains the leading cause of cancer-related mortality worldwide, with many patients presenting with advanced disease at initial diagnosis. Moreover, in spite of recent advances in chemotherapy and targeted therapy, 5-year survival for patients with NSCLC is still disappointingly low at less than 20%. Therefore, it is urgent need to develop effective biomarkers for early diagnosis or new therapeutic target. In this study, we analyzed the association between Bgn expression in TEC in lung cancer and the cancer progression of these patients to evaluate the possibility of Bgn as a biomarker. [Method]: A total 46 patients with lung cancer, who had undergone thoracic surgery at Hokkaido university hospital from February 2015 to March 2017 , were enrolled in this study. First, we performed immunohistochemistry of CD31 and Bgn with serial sections of resected lung tumor tissues, and analyzed the correlation between Bgn positive vessel density in primary lung tumors and clinicopathological factors. Second, we measured the Bgn levels in preoperative serum by ELISA,and the correlation between Bgn positive vessel density in lung tumor tissue and blood Bgn levels. [Result]: The Bgn positive vessel density in primary lung tumor tissue was significantly correlated with primary tumor invasion (p=0.036) and pleural invasion (p=0.036). The preoperative serum Bgn level was also significantly correlated with primary tumor invasion (p=0.0017), pleural invasion (p=0.046) and preoperative blood c-reactive protein level (p=0.012). The Bgn positive vessel density in primary lung tumors was significantly correlated with preoperative serum Bgn level (p<0.0001). In case of lung adenocarcinoma, average of serum Bgn level in Ground Glass Opacity (GGO) positive cases (178ng/ml) was significantly lower than that in GGO negative cases (473ng/ml) (p=0.043). The serum Bgn level was significantly higher in the patients classified into high-grade group (1082ng/ml) by IASLC/ATS/ERS classification than that in intermediate-grade or low-grade groups (264ng/ml, p=0.037). [Conclusion]: In conclusion, these results suggested that Bgn expression in TEC could be a biomarker of lung cancer Citation Format: Hirofumi Morimoto, Nako Maishi, Yasuhiro Hida, Hiroshi Nishihara, Yutaka Hatanaka, Yoshihiro Matsuno, Toru Nakamura, Satoshi Hirano, Kyoko Hida. Biglycan, tumor endothelial secreting proteoglycan, as possible biomarker for lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2574.