摘要
目的分析非小细胞肺癌(NSCLC)组织染色体片段的扩增与缺失,揭示这些异常改变与NSCLC化疗疗效的关系。方法从NSCLC患者石蜡包埋肿瘤组织中提取基因组DNA,以简并寡核苷酸引物PCR扩增并标记探针,采用比较基因组杂交方法,检测染色体片段的扩增和缺失,分析其与NSCLC化疗疗效及其他临床资料的关系。结果样品扩增占96.12%,缺失占3.88%。扩增频率最高区段是19p13.1-13.3(15/34,44.12%),其次为9q12-q22(10/34,29.41%)、22q12-q13(10/34,29.41%)和Xq(11/34,32.35%);化疗敏感者染色体区段变异总数为188,化疗抗拒者染色体区带变异总数为452;化疗敏感与化疗抗拒染色体变异数目差异具有统计学意义(P=0.005)。14p12-p13和19p扩增与化疗敏感相关(P<0.01);1q12-q22(P=0.005)、10q25-q26(P=0.029)、5p15.1-p15.3(P=0.039)、19q13.2-13.4(P=0.029)、20p11.2-p12(P=0.039)、21q22(P=0.016)和Xp21-p22.1(P=0.006)扩增与化疗抗拒密切相关。染色体异常改变与其他临床资料,包括术后较早复发转移和初诊晚期、病理分型、年龄、性别、临床分期(ⅢB和Ⅳ期)无相关性。结论采用比较基因组杂交的方法检测特异性染色体区段的扩增与缺失与以铂类为主的一线化疗疗效关系密切,有助于进一步确立与化疗敏感性相关的具体的功能基因,预测临床化疗疗效,实现个体化治疗。
Objective To explore the association between chromosomal disbalances and chemoresis-tance /chemosensitivity in non-small cell lung cancer(NSCLC)using comparative genomic hybridization(CGH).Methods Genomic DNA samples were prepared from the tumor tissues in paraffin-embedded sec-tions derived from 88 patients with advanced NSCLC(18 with chemosensitivity and 16 with chemoresistance).The DNAs were first amplified by a degenerate oligonucleotide prime-polymerase chain reaction protocol and then labeled with fluorescence as probes for CGH analyses.The correlations of the resulting chromosomal imbal-ances with the chemisensitivity and other pathological features of the patients were analyzed.Results A total of 640 abnormal chromosome regions including 96.12% gains and 3.88% losses were detected in 88 speci-mens.The results indicated that the most frequently gained chromosome regions were 19p13.1-13.3(39 /88,44.12%),followed by 9q12-q22(26 /88,29.41%),22q12-q13(26 /88,29.41%),and Xq(29 /88,32.35%).The total number of abnormal regions related with chemosensitibvity was 188(182 gains and 6 los-ses),while the number of the abnormal regions linked to the chemoresistance was 452(431 gains and 21 los-ses)(P = 0.005).Gains of 14p12-p13 and 19p were significantly correlated with the chemosensitivity of the NSCLC(P = 0.006).Gains of 1q12-q22,10q25-q26,5p15.1-p15.3,19q13.2-13.4,20p11.2-p12,21q22,and Xp21-p22.1 were also significnatly correlated with the chemoresistance(P = 0.005,0.029,0.039,0.029,0.039,0.016,and 0.006,respectively).No correlation between the chromosome abnormal-ities and other clinical features was observed.Conclusions The specific gains and losses of chromosome re-gion is correlated with platinum-based first-line chemotherapy in NSCLC patients,as confirmed by CGH detec-tion.This finding is useful for further identifying the chemosensitivity-related functional genes,predicting clini-cal effectiveness,and achieve individualized treatment in the future.
出处
《中国医学科学院学报》
CAS
CSCD
北大核心
2010年第4期389-393,共5页
Acta Academiae Medicinae Sinicae
基金
国家自然科学基金(30672428)
军队十一五重点课题(06G106)~~
关键词
非小细胞肺癌
染色体异常
比较基因组杂交
化疗抗拒
化疗敏感
non-small cell lung cancer
chromosomal imbalances
comparative genomic hybridization
chemoresistance
chemosensitivity
