摘要
目的探讨基因化疗敏感性与化疗结局之间的关系。方法纳入我院2011年1月1日至2017年12月31日38例,平均年龄16.32岁,男18例,女20例。病变部位:股骨远端25例,胫骨近端9例,肱骨远端2例,髋骨1例,锁骨远端1例,均为普通型骨肉瘤。通过实时PCR和DNA测序,确定患者化疗前样本中化疗相关基因突变和表达程度。检测的基因包括异环磷酰胺相关基因CYP2C9*3,铂类相关基因ERCC1、BRCA1、XRCC1、GSTP1、MRP2和阿霉素相关基因TOP2A、ABCB1、GSTM1、GSTT1等。对PCR和测序结果进行系统性分析来评估患者对化疗药物的敏感性。患者均行异环磷酰胺+铂类+阿霉素化疗方案,通过疼痛、肿瘤大小、肿瘤边界及肿瘤内部是否出现钙化灶评估临床化疗效果。结果个体新辅助化疗结果显示化疗有效率63.2%(24/38)。基因检测分析显示,异环磷酰胺敏感率89.5%(34/38),铂类敏感率81.6%(31/38),阿霉素敏感率57.9%(22/38);基因敏感性中,仅对一种药敏感的患者化疗有效率为0%(0/3),对任意两种药敏感的患者有效率为70%(14/20),三药敏感者有效率为66.7%(10/15)。结论多种化疗药物敏感的患者,其化疗有效率明显高于仅对一种药敏感的患者。但是对于敏感性较差患者的化疗方案该如何调整,还有待后续研究。而且需要通过对更大样本结果的分析来提高研究结果的可信度。
Objective To explore expressions and mutations of chemosensitivity-related genes,and to discuss the correlation between gene and clinical outcomes.Methods This study selected 38 osteosarcoma patients from 2011 to 2017.The mean age was 16.32 years.There were 18 males and 20 females.Location:25 patients in the distal femur,9 patients in the proximal tibia,2 patients in the distal humerus,1 patient in the hip and 1 patient in the distal clavicle.All of them were common osteosarcoma.Expressions and mutations of chemosensitivity-related genes were detected via real time PCR and DNA sequencing,including ifosfamide-related gene(CYP2 C9*3),platinum-related genes(ERCC1,BRCA1,XRCC1,GSTP1,MRP2),and doxorubicin-related genes(TOP2 A,ABCB1,GSTM1,GSTT1).Chemosensitivity was evaluated by a systematical analysis of the results of PCR and DNA sequencing.All patients underwent the same chemotherapy regimen including ifosfamide,platinum and doxorubicin.Clinical outcomes were evaluated by pain,tumor size,tumor boundaries and calcification.Results Neoadjuvant chemotherapy effective rate was 63.2%(24/38).Sensitive rate:ifosfamide 89.5%(34/38);platinum 81.6%(31/38);doxorubicin 57.9%(22/38).Gene sensitivity:sensitive to one drug,effective rate 0%(0/3);sensitive to two or three drugs,effective rate 70%(14/20);sensitive to three drugs,effective rate 66.7%(10/15).Conclusions Patients who are sensitive to multiple drugs have better chemotherapy efficiency than to only one drug.More research is needed on the adjustment of chemotherapy regimen of patients with low sensitivity.Large-scale samples are recommended to enhance the reliability of the conclusion.
作者
龙作尧
鲁亚杰
李明辉
肖鑫
王臻
LONG Zuoycio;LU Ya-jie;LI Ming-hui;XIAO Xin;WANd Zhen(Department of Orthopedics,Xijing Hospital,Air Force Military Medical University,Xi 'an,Shaanxi,710032,China)
出处
《中国骨与关节杂志》
CAS
2019年第3期229-234,共6页
Chinese Journal of Bone and Joint
关键词
骨肉瘤
放化疗
辅助
药物疗法
基因
Osteosarcoma
Chemoradiotherapy,adjuvant
Drug therapy
Gene
