Abstract 4332: Evaluation of arachidonic acid pathways with prognosis in patients with surgically resected non-small cell lung cancer

Abstract

Abstract Background: Arachidonic acid (ARA) is a polyunsaturated fatty acid present in the phospholipids of cell membranes. ARA is metabolized through two major pathways, cyclooxygenase (COX) and lipoxygenase (LOX), resulting in various biologically active eicosanoids, such as prostaglandins, leukotrienes, and hydroxyeicosatetraenoic acids. Cumulative evidence from both in vitro and animal studies suggests that COX and LOX pathways may be involved in the development and progression of lung cancer by regulating multiple biological processes. However, no direct evidence exists to connect key enzymes of COX and LOX pathways with prognosis of non-small cell lung cancer (NSCLC). We conducted a study to evaluate the association of protein expression of major enzymes in the COX and LOX pathways with prognosis of NSCLC. Materials and Methods: Included in the study are 98 patients with surgically resected NSCLC. The archived paraffin-embedded tumor tissue blocks were retrieved, and tissue microarray were constructed with at least two cores for most cases. Clinical data were obtained from medical records. Expression levels of COX-2, 12-LOX, 15-LOX-1, 15-LOX-2, 5-LOX activating protein (FLAP), and 11β-hydroxysteroid dehydrogenase type I (11βHSD1) and type II (11βHSD2) were evaluated immunohistochemically. Odds ratios (OR) of death were estimated using logistic regression models with adjustment for age at diagnosis, BMI, smoking status, and tumor stage. Results: All seven assayed markers were significantly correlated with one another (r = 0.299 - 0.658, P < 0.01). We observed that a higher level of COX-2 protein expression was associated with advanced tumor stage (P = 0.026). A higher level of 15-LOX-1 protein expression was associated with significantly increased risk of death (OR = 3.27, 95% CI 1.01 - 10.5, P = 0.048) and a higher level of 11βHSD1 protein expression was associated with a marginally significant increased risk of death (OR = 2.67, 95% CI 0.86 - 8.31, P = 0.089). No association of other markers with lung cancer death was found. Conclusions: 15-LOX-1 and 11βHSD1 may be prognostic markers for NSCLC. Validation of the findings in an independent patient cohort is warranted. Citation Format: Yinghao Su, Ming-Zhi Zhang, Wanqing Wen, Wei Zheng, Rosana Eisenberg, Pierre P. Massion, Qiuyin Cai. Evaluation of arachidonic acid pathways with prognosis in patients with surgically resected 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 4332. doi:10.1158/1538-7445.AM2015-4332