Raf激酶抑制蛋白预测鼻咽癌放疗敏感性

Predicting the radiosensitivity with Raf kinase inhibitor protein in nasopharyngeal carcinoma

目的 探讨鼻咽癌（NPC）肿瘤组织中Raf激酶抑制蛋白（RKIP）表达与NPC放疗敏感性的关系,评估其预测NPC患者放疗敏感性的价值.方法 采用回顾性研究,收集病理确诊为NPC且初治时无远处转移及只接受根治性调强放疗的180例患者.以放疗开始5年内鼻咽原发灶和（或）颈部转移灶的照射野内出现复发为放疗抗拒组,均有病理活检证实,且与放疗前病理类型相同；放疗开始5年内鼻咽原发灶和颈部转移灶射野内均未出现复发的NPC患者为放疗敏感组.两组患者以放疗敏感性密切相关的重要因素进行配对.免疫组织化学法检测所有入组患者在接受放疗前肿瘤组织的RKIP,分析其与放疗敏感性的关系.结果 放疗敏感组及放疗抗拒组RKIP阳性表达率（80.0％与26.7％）及表达强度差异均有统计学意义（x2=12.498、51.429,P＜0.01）,且均与放疗抵抗呈负相关（r=-0.535、-0.344,P＜0.01）.RKIP判别放疗抵抗的指标敏感性80.0％,特异性73.3％,准确率77.2％,阳性预测值75.0％,阴性预测值78.6％,假阳性率26.7％,假阴性率20.0％.结论 RKIP与NPC放疗抵抗呈负相关,可作为一种NPC患者内在放射敏感性的初筛分子标记物,有待前瞻性研究进一步证实.

Objective To investigate the relationship between RKIP expression and the efficiency of radiotherapy in NPC patients and evaluate the possibility of using RKIP as a predictor of radiosensitivity.Methods A total of 180 patients with NPC in Sun Yat-sen University Cancer Center without evidence of distant metastasis at initial diagnosis were enrolled in this study,who had received intensity-modulated radiotherapy alone.Patients were classified into 2 groups according to criteria below：patients with biopsy proven recurrent diseases occurring at nasopharynx and/or neck within 5 years after radiotherapy were classified as the radioresistant group.The pathological type at relapse was the same as the previous one before treatment.Patients with a minimum follow-up of 5 years after radiotherapy without evidence of recurrence at the original site of the tumor were classified as the radiosensitive group.Patients in the 2 groups were matched according to the factors related with radiosensitivity.RKIP was examined by immunohistochemical staining before radiotherapy.The relationship between RKIP expression and the effect of radiotherapy were analyzed.Results The positive rate of the RKIP expression in the radiosensitive group versus the radioresistant group was 80.0% versus 26.7%.The positive rate （x2 =12.498,P 〈0.01） and the intensity of the RKIP expression （x2 =51.429,P 〈 0.01） were significantly different between 2 groups with a negative correlation with radio-resistance to NPC （r =-0.344,-0.535,respectively,P 〈 0.01）.Based on the RKIP expression,the radiosensitivity,specificity,accuracy,positive predictive value,negative predictive value,false positive and false negative were predicted as follows：80.0%,73.3%,77.2%,75.0%,78.6%,26.7%,and 20.0%,respectively.Conclusions RKIP protein shows negative correlation with radioresistance to NPC and could serve as a biomarker in preliminarily screening the intrinsic radiosensitivity of NPC.