| Title | Co-expression modules of NF1, PTEN and sprouty enable distinction of adult diffuse gliomas according to pathway activities of receptor tyrosine kinases |
| Authors | Zhang, Wanyu Lv, Yuhong Xue, Yang Wu, Chenxing Yao, Kun Zhang, Chuanbao Jin, Qiang Huang, Rong Li, Jiuyi Sun, Yingyu Su, Xiaodong Jiang, Tao Fan, Xiaolong |
| Affiliation | Beijing Normal Univ, Beijing Key Lab Gene Resources & Mol Dev, Lab Neurosci & Brain Dev, Beijing, Peoples R China. Beijing Sanbo Brain Hosp, Capital Med Univ, Dept Neurosurg, Beijing, Peoples R China. Capital Med Univ, Beijing Sanbo Brain Hosp, Dept Pathol, Beijing, Peoples R China. Capital Med Univ, Beijing Neurosurg Inst, Beijing, Peoples R China. Capital Med Univ, Beijing Tiantan Hosp, Dept Neurosurg, Beijing, Peoples R China. Peking Univ, Sch Life Sci, Biodynam Opt Imaging Ctr BIOPIC, Beijing, Peoples R China. Hebei Med Univ, Dept Cell Biol, Shijiazhuang, Hebei, Peoples R China. |
| Keywords | glioma molecular classification receptor tyrosine kinase HUMAN GLIOBLASTOMA CELLS HIGH-GRADE GLIOMA TUMOR ANGIOGENESIS MALIGNANT GLIOMAS HUMAN-DISEASE EXPRESSION PROGRESSION LANDSCAPE PDGFRA EGFR |
| Issue Date | 2016 |
| Publisher | ONCOTARGET |
| Citation | ONCOTARGET.2016,7(37),59098-59114. |
| Abstract | Inter-individual variability causing elevated signaling of receptor tyrosine kinases (RTK) may have hampered the efficacy of targeted therapies. We developed a molecular signature for clustering adult diffuse gliomas based on the extent of RTK pathway activities. Glioma gene modules co-expressed with NF1 (NF1-M), Sprouty (SPRY-M) and PTEN (PTEN-M) were identified, their signatures enabled robust clustering of adult diffuse gliomas of WHO grades II-IV from five independent data sets into two subtypes with distinct activities of RAS-RAF-MEK-MAPK cascade and PI3KAKT pathway (named RMPA(high) and RMPA(low) subtypes) in a morphology-independent manner. The RMPA(high) gliomas were associated with poor prognosis compared to the RMPA(low) gliomas. The RMPA(high) and RMPA(low) glioma subtypes harbored unique sets of genomic alterations in the RTK signaling-related genes. The RMPA(high) gliomas were enriched in immature vessel cells and tumor associated macrophages, and both cell types expressed high levels of pro-angiogenic RTKs including MET, VEGFR1, KDR, EPHB4 and NRP1. In gliomas with major genomic lesions unrelated to RTK pathway, high RMPA signature was associated with short survival. Thus, the RMPA signatures capture RTK activities in both glioma cells and glioma microenvironment, and RTK signaling in the glioma microenvironment contributes to glioma progression. |
| URI | http://hdl.handle.net/20.500.11897/493531 |
| ISSN | 1949-2553 |
| DOI | 10.18632/oncotarget.10359 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 生命科学学院 |
