Pinel Baptiste, Duchesne Mathilde, Godet Julie, Milin Serge, Berger Antoine, Wager Michel, Karayan-Tapon Lucie
CHU de Poitiers Department of Cancer Biology, Université de Poitiers, Poitiers, France.
CHU de Poitiers Department of Radiotherapy, Université de Poitiers, Poitiers, France.
J Neurooncol. 2017 Apr;132(2):287-294. doi: 10.1007/s11060-016-2367-7. Epub 2017 Jan 10.
A better understanding of the relationship between glioblastomas molecular subtypes and radio-chemotherapy is needed for the development of individualized strategies. In this study, we aimed to assess whether non-homologous end-joining (NHEJ) protein expression is associated and could predict responses to treatment of mesenchymal (MES) and proneural (PN) subtypes. Tumors from 122 patients with a glioblastoma treated at the University Hospital of Poitiers between 2002-2013 by an association of radiotherapy and temozolomide were collected. Among these tumors, 80 were suitable for in situ analysis and were included in TissueMicroArray. The expression of DNA-PKcs, Ku70, Ku80 and CD44, Olig2 (respectively surrogate markers of MES and PN subtypes) were evaluated by immunohistochemistry. The median survival of patients with high and low CD44 expression was 11.9 months (95% CI 7.7-14) and 19.1 months (95% CI 15.2-22.4) respectively (p = 0.008). Median survival of patients with high and low DNA-PKcs levels was 20.0 months (95% CI 15.2-25.3) and 12.9 months (95% CI 9.9-19.5) respectively (p = 0.036). High levels of Olig2, Ku70 and Ku80 tended to be associated with better overall survival but no significant differences were found. Overall survival of class I patients (CD44+ and DNA-PKcs+) was longer than class II (CD44+ and DNA-PKcs- or CD44- and DNA-PKcs+) and class III (CD44- and DNA-PKcs-), (p = 0.005 and 0.003 respectively). High levels of CD44 and DNA-PK are associated with a better survival and better response to radiotherapy and temozolomide and could establish prognosis classes by predicting survival and response to therapy for GBMs patients.
为了制定个体化治疗策略，需要更好地了解胶质母细胞瘤分子亚型与放化疗之间的关系。在本研究中，我们旨在评估非同源末端连接（NHEJ）蛋白表达是否与间充质（MES）和神经前体细胞（PN）亚型的治疗反应相关，并能否预测其治疗反应。收集了2002年至2013年在普瓦捷大学医院接受放疗和替莫唑胺联合治疗的122例胶质母细胞瘤患者的肿瘤组织。其中80例适合原位分析，并被纳入组织微阵列。通过免疫组织化学评估DNA-PKcs、Ku70、Ku80以及CD44、Olig2（分别为MES和PN亚型的替代标志物）的表达。CD44高表达和低表达患者的中位生存期分别为11.9个月（95%CI 7.7-14）和19.1个月（95%CI 15.2-22.4）（p = 0.008）。DNA-PKcs高水平和低水平患者的中位生存期分别为20.0个月（95%CI 15.2-25.3）和12.9个月（95%CI 9.9-19.5）（p = 0.036）。Olig2、Ku70和Ku80的高水平往往与更好的总生存期相关，但未发现显著差异。I类患者（CD44+和DNA-PKcs+）的总生存期长于II类（CD44+和DNA-PKcs-或CD44-和DNA-PKcs+）和III类（CD44-和DNA-PKcs-）患者（分别为p = 0.005和0.003）。CD44和DNA-PK的高水平与更好的生存期以及对放疗和替莫唑胺的更好反应相关，并且可以通过预测胶质母细胞瘤患者的生存期和治疗反应来建立预后分类。
