Co-expression of COX-2 and 5-LO in primary glioblastoma is associated with poor prognosis.
Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LO) are important factors in tumorigenesis and malignant progression; however, studies of their roles in glioblastoma have produced conflicting results. To define the frequencies of COX-2 and 5-LO expression and their correlation with clinicopathological features and prognosis, tumor tissues from 76 cases of newly diagnosed primary ordinary glioblastoma were examined for COX-2 and 5-LO expression by immunohistochemistry. The expression levels of COX-2 and 5-LO and the relationships between the co-expression of COX-2/5-LO and patient age and gender, edema index (EI), Karnofsky Performance Scale and overall survival (OS) were analyzed. COX-2 and 5-LO were expressed in 73.7 % (56/76) and 92.1 % (70/76) of the samples, respectively. Among the clinicopathological characteristics, only age (>60 years) exhibited a significant association with the high expression of COX-2. No statistically significant correlations were found in the 5-LO cohort. A significant positive correlation was revealed between the COX-2 and 5-LO scores (r = 0.374; p = 0.001). The elevated co-expression of COX-2 and 5-LO was observed primarily in the patients over the age of 60 years. Patients with a high expression of COX-2 had a significantly shorter OS (p < 0.01), whereas the immunoexpression of 5-LO was not associated with the OS of patients with glioblastoma. Survival analysis indicated that simultaneous high levels of COX-2 and 5-LO expression were significantly correlated with poor OS and, conversely, that a low/low expression pattern of these two proteins was significantly associated with better OS (p < 0.05). Moreover, the Cox multivariable proportional hazard model showed that a high expression of COX-2, high co-expression of COX-2 and 5-LO, and a high Ki-67 index were significant predictors of shorter OS in primary glioblastoma, independent of age, gender, EI, 5-LO expression and p53 status. The hazard ratios for OS were 2.347 (95 % CI 1.30-4.25, p = 0.005), 1.900 (95 % CI 1.30-2.78, p = 0.001), and 2.210 (95 % CI 1.19-4.09, p = 0.011), respectively. These results suggest that COX-2 and 5-LO play roles in tumorigenesis and the progression of primary glioblastoma and that the co-expression pattern of COX-2/5-LO may be used as an independent prognostic factor in this disease.
Department of Pathology, The First Affiliated Hospital of Fujian Medical University, No. 20 Chazhong Road, Taijiang Ditrict, Fuzhou City, 350005, China. wang_xfu@126.com.
Xingfu
X
Wang
Department of Pathology, The First Affiliated Hospital of Fujian Medical University, No. 20 Chazhong Road, Taijiang Ditrict, Fuzhou City, 350005, China. fychyp@126.com.
Yupeng
Y
Chen
Department of Pathology, The First Affiliated Hospital of Fujian Medical University, No. 20 Chazhong Road, Taijiang Ditrict, Fuzhou City, 350005, China. zhgshg@126.com.
Sheng
S
Zhang
Department of Endocrinology, Fujian Province Governmental Hospital, No. 67 Guping Road, Gulou Ditrict, Fuzhou City, 350003, China. fzzhlf@126.com.
Lifeng
L
Zhang
Department of Pathology, The First Affiliated Hospital of Fujian Medical University, No. 20 Chazhong Road, Taijiang Ditrict, Fuzhou City, 350005, China. lxy370681711@163.com.
Xueyong
X
Liu
Department of Pathology, The First Affiliated Hospital of Fujian Medical University, No. 20 Chazhong Road, Taijiang Ditrict, Fuzhou City, 350005, China. 2424465020@qq.com.
Li
L
Zhang
Department of Pathology, The First Affiliated Hospital of Fujian Medical University, No. 20 Chazhong Road, Taijiang Ditrict, Fuzhou City, 350005, China. 704038681@qq.com.
Xiaoling
X
Li
Department of Pathology, The First Affiliated Hospital of Fujian Medical University, No. 20 Chazhong Road, Taijiang Ditrict, Fuzhou City, 350005, China. cdy199090@163.com.
Dayang
D
Chen
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D001932:Brain Neoplasms / Q000175:diagnosis / Q000201:enzymology*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000175:diagnosis / Q000201:enzymology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D013223:Statistics as Topic; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D055815:Young Adult
D001094:Arachidonate 5-Lipoxygenase; D051546:Cyclooxygenase 2
5-LO; COX-2; Glioblastoma; Immunohistochemistry; Prognosis