Xian-Xin Qiu1, Long Chen2, Chen-Hong Wang3, Zhi-Xiong Lin4, Bi-Juan Chen5, Na You6, Yao Chen3, Xing-Fu Wang7. 1. Tumor Invasion Microecological Laboratory, Fujian Medical University, Fuzhou, Fujian, China; Department of Neurosurgery, the Children's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. 2. Tumor Invasion Microecological Laboratory, Fujian Medical University, Fuzhou, Fujian, China; Intensive Care Unit, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China. 3. Tumor Invasion Microecological Laboratory, Fujian Medical University, Fuzhou, Fujian, China. 4. Tumor Invasion Microecological Laboratory, Fujian Medical University, Fuzhou, Fujian, China; Department of Neurosurgery, Beijing Sanbo Brain Hospital, Capital Medical University, Beijing, China. Electronic address: lzx1967@sina.com. 5. Tumor Invasion Microecological Laboratory, Fujian Medical University, Fuzhou, Fujian, China; Department of Radiation Oncology, Fujian Provincial Cancer Hospital, Fuzhou, Fujian, China. 6. Tumor Invasion Microecological Laboratory, Fujian Medical University, Fuzhou, Fujian, China; Department of Rehabilitation, Fujian Provincial Hospital, Fuzhou, Fujian, China. 7. Department of Pathology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
Abstract
PURPOSE: Delta-like ligand 4 (DLL4) and Jagged1 (JAG1), 2 vascular Notch ligands, are involved in the process of tumor angiogenesis. The present study investigates their relationship with microvascularization and the prognostic effect in primary glioblastoma. METHODS: Tumor tissues from 61 glioblastomas were analyzed using immunohistochemistry for DLL4/JAG1 expression and microvascular formations. The correlations between DLL4/JAG1 and microvascularization were analyzed. The survival probabilities were computed using the Kaplan-Meier method. The Cox proportional hazards regression model was used for multivariate analysis of time to progression (TTP) and overall survival (OS). RESULTS: The results showed increased DLL4 and JAG1 expression in glioblastoma tissues. Five types of basic microvascular formations, including microvascular sprouting, vascular cluster, vascular garland, glomeruloid vascular proliferation, and vasculogenic mimicry, were detected. Glioblastomas with the type I microvascular pattern (MVP) that displayed prominent microvascular sprouting and vascular clusters tended to have higher DLL4 expression, whereas those with the type II MVP that had numerous vascular garlands, glomeruloid vascular proliferations, and vasculogenic mimicries showed upregulated JAG1 expression. Univariate analysis documented that high DLL4 expression, high JAG1 expression, and type II (MVP) were statistically associated with reduced TTP and OS. Multivariate analysis confirmed high DLL4 expression, high JAG1 expression, and type II MVP as significant prognostic factors for both shorter TTP and OS, independent of age, Karnofsky performance scale, and other molecular markers (vascular endothelial growth factor, Ki67, and P53). CONCLUSIONS: DLL4 and JAG1 may have opposing effects on tumor angiogenesis in glioblastoma. The Notch pathway may be a new target for antiangiogenic therapy in glioblastoma.
PURPOSE:Delta-like ligand 4 (DLL4) and Jagged1 (JAG1), 2 vascular Notch ligands, are involved in the process of tumor angiogenesis. The present study investigates their relationship with microvascularization and the prognostic effect in primary glioblastoma. METHODS:Tumor tissues from 61 glioblastomas were analyzed using immunohistochemistry for DLL4/JAG1 expression and microvascular formations. The correlations between DLL4/JAG1 and microvascularization were analyzed. The survival probabilities were computed using the Kaplan-Meier method. The Cox proportional hazards regression model was used for multivariate analysis of time to progression (TTP) and overall survival (OS). RESULTS: The results showed increased DLL4 and JAG1 expression in glioblastoma tissues. Five types of basic microvascular formations, including microvascular sprouting, vascular cluster, vascular garland, glomeruloid vascular proliferation, and vasculogenic mimicry, were detected. Glioblastomas with the type I microvascular pattern (MVP) that displayed prominent microvascular sprouting and vascular clusters tended to have higher DLL4 expression, whereas those with the type II MVP that had numerous vascular garlands, glomeruloid vascular proliferations, and vasculogenic mimicries showed upregulated JAG1 expression. Univariate analysis documented that high DLL4 expression, high JAG1 expression, and type II (MVP) were statistically associated with reduced TTP and OS. Multivariate analysis confirmed high DLL4 expression, high JAG1 expression, and type II MVP as significant prognostic factors for both shorter TTP and OS, independent of age, Karnofsky performance scale, and other molecular markers (vascular endothelial growth factor, Ki67, and P53). CONCLUSIONS:DLL4 and JAG1 may have opposing effects on tumor angiogenesis in glioblastoma. The Notch pathway may be a new target for antiangiogenic therapy in glioblastoma.
Authors: Shuya Zhang; Ji Young Kim; Suowen Xu; Huan Liu; Meimei Yin; Marina Koroleva; Jia Guo; Xiuying Pei; Zheng Gen Jin Journal: Proc Natl Acad Sci U S A Date: 2020-02-19 Impact factor: 12.779
Authors: Yoshihiro Otani; Ji Young Yoo; Samantha Chao; Joseph Liu; Alena Cristina Jaime-Ramirez; Tae Jin Lee; Brian Hurwitz; Yuanqing Yan; Hongsheng Dai; Joseph C Glorioso; Michael A Caligiuri; Jianhua Yu; Balveen Kaur Journal: Clin Cancer Res Date: 2020-03-05 Impact factor: 12.531