Abstract 1547: The clinical implication of MMP-1 and TIMP-1 on prognosis in patients with non-small cell lung cancer

Introduction: The interaction between tumor cells and tumor micro-environment (TME) plays important role in tumor initiation, progression, treatment resistance, and prognosis in solid tumors including non-small cell lung cancer (NSCLC). The aim of this study is to evaluate the prognostic role of TME-related molecules in NSCLC patients who received surgical resection. To find out a possibility of a potential serum biomarker, protein expression in tissue from surgical specimen and pre-operative serum were investigated together. Methods: For 85 NSCLC patients who underwent surgical resection from August 2006 to September 2010 and had pre-operative serum samplings, we screened the serum levels of 60 TME-related molecules with angiogenesis array kit for 8 patients who had recurrences and 4 patients who did not. For matrix metalloproteinase (MMP)-1 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 in which significant difference was observed between recurrence and recurrence-free groups, protein expressions were investigated using ELISA in serum and immunohistochemistry in tumor tissue. Results: High serum MMP-1 was related to carcinoembryonic antigen (CEA) level≥5 at diagnosis (P = 0.034), higher frequency of the presence of vascular invasion (P = 0.041). High expression of MMP-1 in tumor cells (intensity score≥2) was related to tumor differentiation (P = 0.057), whereas high MMP-1 expression in stroma was significantly associated with lymph node metastasis and TNM stage (P = 0.021 and P = 0.022, respectively). In the case of TIMP-1, expression in tumor cells was higher for adenocarcinoma but higher in stromal cells for squamous cell carcinoma (P = 0.046). There was no correlation between the tissue and serum levels of MMP-1 and TIMP-1. High serum MMP-1 showed a trend for short overall survival (P = 0.080). When serum MMP-1 was combined with CEA level or presence of vascular invasion, the prognostic implication for overall survival was statistically significant. Neither tumor nor stromal positivity for MMP-1 and TIMP-1 was associated with survival outcome; however, a tumor/stroma TIMP-1 intensity ratio≥1 was strongly associated with early recurrence in multivariate analysis (HR = 13.1, P = 0.008). Conclusion: In surgically resected NSCLC patients, serum MMP-1 showed a possibility as a prognostic biomarker. In addition, the tumor/stroma TIMP-1 ratio (≥1) in tissue may be a useful to predict tumor recurrence. Citation Format: Ho Jung An, Jin-Hyoung Kang, Yoon-Jin Lee, Soon Uk Hong, Kyo Young Lee, Jeong-Oh Kim. The clinical implication of MMP-1 and TIMP-1 on prognosis in patients with non-small cell lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1547. doi:10.1158/1538-7445.AM2015-1547