Tabouret E, Labussière M, Alentorn A, Schmitt Y, Marie Y, Sanson M
Sorbonne Universités, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, INSERM U1127, CNRS UMR 7225, UPMC Paris 06, Paris 75013, France; AP-HP, Service de Neurologie 2, Groupe Hospitalier Pitié-Salpêtrière, Paris 75013, France.
Sorbonne Universités, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, INSERM U1127, CNRS UMR 7225, UPMC Paris 06, Paris 75013, France.
J Neurol Sci. 2015 Nov 15;358(1-2):440-3. doi: 10.1016/j.jns.2015.09.345. Epub 2015 Sep 11.
Deletion of the tumor suppressor gene LRP1B has been reported in glioblastoma, the most aggressive primary brain tumor in adults. Our objective was to analyze frequency and prognostic impact of LRP1B deletion and expression levels.
We retrospectively included all the primary IDH1/2 wild-type GBM patients with available clinical follow-up, DNA and RNA from our database. Deletions were analyzed by SNP-array. LRP1B mRNA expression was analyzed by reverse transcription quantitative polymerase chain reaction.
178 patients were included with a median age of 62.36 years. LRP1B deletions were observed for 10.1% of patients (complete: 2.8%, partial: 7.3%). LRP1B deletions were associated with poor progression-free survival (PFS) (p=0.004) and overall survival (OS) (p=0.001). By multivariate analysis, LRP1B deletions remained significant for both PFS (p=0.003, hazard ratio (HR): 2.261) and OS (p=0.001, HR: 2.609). LRP1B was down expressed with a mean relative expression of 46% comparatively to normal tissue. No association between LRP1B mRNA and patient outcome was observed. No correlation was found between the deletions and the mRNA down-expression. These results were validated using GBM TCGA data.
LRP1B presents with frequent molecular alterations which impact patient outcome, highlighting the potential interest of this gene for glioblastoma patients.
据报道，在成人大脑中最具侵袭性的原发性脑肿瘤胶质母细胞瘤中，肿瘤抑制基因LRP1B存在缺失情况。我们的目的是分析LRP1B缺失的频率及其对预后的影响以及其表达水平。
我们回顾性纳入了数据库中所有有可用临床随访资料、DNA和RNA的原发性异柠檬酸脱氢酶1/2（IDH1/2）野生型胶质母细胞瘤患者。通过单核苷酸多态性阵列（SNP-array）分析缺失情况。通过逆转录定量聚合酶链反应分析LRP1B mRNA表达。
纳入178例患者，中位年龄为62.36岁。10.1%的患者观察到LRP1B缺失（完全缺失：2.8%，部分缺失：7.3%）。LRP1B缺失与无进展生存期（PFS）差（p = 0.004）和总生存期（OS）差（p = 0.001）相关。通过多变量分析，LRP1B缺失对PFS（p = 0.003，风险比（HR）：2.261）和OS（p = 0.001，HR：2.609）均仍具有显著意义。与正常组织相比，LRP1B表达下调，平均相对表达为46%。未观察到LRP1B mRNA与患者预后之间的关联。未发现缺失与mRNA下调表达之间的相关性。这些结果使用胶质母细胞瘤癌症基因组图谱（GBM TCGA）数据得到了验证。
LRP1B存在频繁的分子改变，这会影响患者预后，突出了该基因对胶质母细胞瘤患者的潜在研究价值。
