Duregon Eleonora, Senetta Rebecca, Pittaro Alessandra, Verdun di Cantogno Ludovica, Stella Giulia, De Blasi Pierpaolo, Zorzetto Michele, Mantovani Cristina, Papotti Mauro, Cassoni Paola
Department of Oncology, University of Torino at San Luigi Hospital, Orbassano, Turin, Italy.
Department of Medical Sciences, University of Torino, Italy.
Oncotarget. 2015 Oct 6;6(30):29626-36. doi: 10.18632/oncotarget.4988.
Brain metastases develop in one-third of patients with non-small-cell lung cancer and are associated with a dismal prognosis, irrespective of surgery or chemo-radiotherapy. Pathological markers for predicting outcomes after surgical resection and radiotherapy responsiveness are still lacking. Caveolin 1 has been associated with chemo- and radioresistance in various tumors, including non-small-cell lung cancer. Here, caveolin 1 expression was assessed in a series of 69 brain metastases from non-small-cell lung cancer and matched primary tumors to determine its role in predicting survival and radiotherapy responsiveness. Only caveolin 1 expression in brain metastasis was associated with poor prognosis and an increased risk of death (log rank test, p = 0.015). Moreover, in the younger patients (median age of <54 years), caveolin 1 expression neutralized the favorable effect of young age on survival compared with the older patients. Among the radiotherapy-treated patients, an increased risk of death was detected in the group with caveolin 1-positive brain metastasis (14 out of 22 patients, HR=6.839, 95% CI 1.849 to 25.301, Wald test p = 0.004). Overall, caveolin 1 expression in brain metastasis from non-small-cell lung cancer is independently predictive of worse outcome and radioresistance and could become an additional tool for personalized therapy in the critical subset of brain-metastatic non-small-cell lung cancer patients.
三分之一的非小细胞肺癌患者会发生脑转移，且无论手术或放化疗如何，其预后都很差。目前仍缺乏用于预测手术切除后结果及放疗反应性的病理标志物。小窝蛋白1（Caveolin 1）在包括非小细胞肺癌在内的多种肿瘤中都与化疗和放疗耐药相关。在此，对69例非小细胞肺癌脑转移瘤及配对的原发肿瘤进行了小窝蛋白1表达评估，以确定其在预测生存及放疗反应性方面的作用。仅脑转移瘤中的小窝蛋白1表达与预后不良及死亡风险增加相关（对数秩检验，p = 0.015）。此外，在较年轻患者（中位年龄<54岁）中，与老年患者相比，小窝蛋白1表达抵消了年轻对生存的有利影响。在接受放疗的患者中，小窝蛋白1阳性脑转移瘤组的死亡风险增加（22例患者中有14例，HR = 6.839，95% CI为1.849至25.301，Wald检验p = 0.004）。总体而言，非小细胞肺癌脑转移瘤中的小窝蛋白1表达可独立预测更差的结果及放疗耐药，并且可能成为脑转移非小细胞肺癌关键亚组患者个性化治疗的额外工具。
