中华妇产科杂志
中華婦產科雜誌
중화부산과잡지
CHINESE JOUNAL OF OBSTETRICS AND GYNECOLOGY
2013年
11期
847-852
,共6页
齐冰丽%李琰%王娜%周荣秒%胡佩%康山
齊冰麗%李琰%王娜%週榮秒%鬍珮%康山
제빙려%리염%왕나%주영초%호패%강산
卵巢肿瘤%DNA结合蛋白质类%内切核酸酶类%多态性,单核苷酸%铂类%预后
卵巢腫瘤%DNA結閤蛋白質類%內切覈痠酶類%多態性,單覈苷痠%鉑類%預後
란소종류%DNA결합단백질류%내절핵산매류%다태성,단핵감산%박류%예후
Ovarian neoplasms%DNA-binding proteins%Endonucleases%Polymorphism,single nucleotide%Platinum%Prognosis
目的 探讨切除修复交叉互补基因1(ERCC1)的单核苷酸多态性(SNP)与卵巢上皮性癌(卵巢癌)患者铂类药物化疗敏感性和预后的关系.方法 通过Haploview软件(Version4.2;http://www.broadinstitute.org)筛选出ERCC1基因的6个标签SNP(tagSNP)位点,即rsl1615、rs3212986、rs735482、rs3212955、rs12610134、rs3212958位点,采用单碱基延伸(Snapshot)法检测220例卵巢癌患者ERCC1基因6个tagSNP位点的基因型.比较铂类药物敏感(147例)和不敏感(73例)、复发(135例)和未复发(85例)、死亡(92例)和存活(128例)患者的ERCC1基因6个tagSNP位点的基因型频率;并对携带ERCC1基因6个tagSNP位点不同基因型的卵巢癌患者的预后进行比较,评价患者预后的指标包括疾病无进展生存时间(PFS)和总生存时间(OS).结果 ERCC1基因rs1615位点CC、CT、TT基因型频率,铂类药物敏感(分别为53.1％、45.6％、1.4％)与不敏感(分别为52.0％、35.6％、12.3％)、复发(分别为54.8％、37.0％、8.2％)与未复发(分别为49.4％、50.6％、0)、死亡(分别为51.1％、39.1％、9.8％)与存活(分别为53.9％、44.5％、1.6％)患者分别比较,差异均有统计学意义(P＜0.05);与携带CC基因型的卵巢癌患者相比,携带TT基因型患者的铂类药物化疗敏感性明显降低(OR =6.22,95％CI为1.12 ～34.42).log-rank分析显示,ERCCl基因rs11615位点CC、CT、TT基因型频率与卵巢癌患者的PFS和OS均明显相关(P ＜0.01);Cox比例风险回归模型分析表明,与携带CC基因型的卵巢癌患者相比,携带TT基因型患者的PFS(分别为21.1、8.6个月;HR =2.19,95％ CI为1.14 ～4.22,P=0.009)和OS(分别为28.5、19.3个月;HR =2.22,95％ CI为1.06 ～4.64,P =0.021)均明显缩短.而另外5个tagSNP(即rs3212986、rs735482、rs3212955、rs12610134、rs3212958)位点的基因型分布与卵巢癌患者的化疗敏感性及预后均无关(P＞0.05).结论ERCC1基因rs11615位点的SNP可能成为预测卵巢癌患者铂类药物化疗敏感性及预后的分子标志物
目的 探討切除脩複交扠互補基因1(ERCC1)的單覈苷痠多態性(SNP)與卵巢上皮性癌(卵巢癌)患者鉑類藥物化療敏感性和預後的關繫.方法 通過Haploview軟件(Version4.2;http://www.broadinstitute.org)篩選齣ERCC1基因的6箇標籤SNP(tagSNP)位點,即rsl1615、rs3212986、rs735482、rs3212955、rs12610134、rs3212958位點,採用單堿基延伸(Snapshot)法檢測220例卵巢癌患者ERCC1基因6箇tagSNP位點的基因型.比較鉑類藥物敏感(147例)和不敏感(73例)、複髮(135例)和未複髮(85例)、死亡(92例)和存活(128例)患者的ERCC1基因6箇tagSNP位點的基因型頻率;併對攜帶ERCC1基因6箇tagSNP位點不同基因型的卵巢癌患者的預後進行比較,評價患者預後的指標包括疾病無進展生存時間(PFS)和總生存時間(OS).結果 ERCC1基因rs1615位點CC、CT、TT基因型頻率,鉑類藥物敏感(分彆為53.1％、45.6％、1.4％)與不敏感(分彆為52.0％、35.6％、12.3％)、複髮(分彆為54.8％、37.0％、8.2％)與未複髮(分彆為49.4％、50.6％、0)、死亡(分彆為51.1％、39.1％、9.8％)與存活(分彆為53.9％、44.5％、1.6％)患者分彆比較,差異均有統計學意義(P＜0.05);與攜帶CC基因型的卵巢癌患者相比,攜帶TT基因型患者的鉑類藥物化療敏感性明顯降低(OR =6.22,95％CI為1.12 ～34.42).log-rank分析顯示,ERCCl基因rs11615位點CC、CT、TT基因型頻率與卵巢癌患者的PFS和OS均明顯相關(P ＜0.01);Cox比例風險迴歸模型分析錶明,與攜帶CC基因型的卵巢癌患者相比,攜帶TT基因型患者的PFS(分彆為21.1、8.6箇月;HR =2.19,95％ CI為1.14 ～4.22,P=0.009)和OS(分彆為28.5、19.3箇月;HR =2.22,95％ CI為1.06 ～4.64,P =0.021)均明顯縮短.而另外5箇tagSNP(即rs3212986、rs735482、rs3212955、rs12610134、rs3212958)位點的基因型分佈與卵巢癌患者的化療敏感性及預後均無關(P＞0.05).結論ERCC1基因rs11615位點的SNP可能成為預測卵巢癌患者鉑類藥物化療敏感性及預後的分子標誌物
목적 탐토절제수복교차호보기인1(ERCC1)적단핵감산다태성(SNP)여란소상피성암(란소암)환자박류약물화료민감성화예후적관계.방법 통과Haploview연건(Version4.2;http://www.broadinstitute.org)사선출ERCC1기인적6개표첨SNP(tagSNP)위점,즉rsl1615、rs3212986、rs735482、rs3212955、rs12610134、rs3212958위점,채용단감기연신(Snapshot)법검측220례란소암환자ERCC1기인6개tagSNP위점적기인형.비교박류약물민감(147례)화불민감(73례)、복발(135례)화미복발(85례)、사망(92례)화존활(128례)환자적ERCC1기인6개tagSNP위점적기인형빈솔;병대휴대ERCC1기인6개tagSNP위점불동기인형적란소암환자적예후진행비교,평개환자예후적지표포괄질병무진전생존시간(PFS)화총생존시간(OS).결과 ERCC1기인rs1615위점CC、CT、TT기인형빈솔,박류약물민감(분별위53.1％、45.6％、1.4％)여불민감(분별위52.0％、35.6％、12.3％)、복발(분별위54.8％、37.0％、8.2％)여미복발(분별위49.4％、50.6％、0)、사망(분별위51.1％、39.1％、9.8％)여존활(분별위53.9％、44.5％、1.6％)환자분별비교,차이균유통계학의의(P＜0.05);여휴대CC기인형적란소암환자상비,휴대TT기인형환자적박류약물화료민감성명현강저(OR =6.22,95％CI위1.12 ～34.42).log-rank분석현시,ERCCl기인rs11615위점CC、CT、TT기인형빈솔여란소암환자적PFS화OS균명현상관(P ＜0.01);Cox비례풍험회귀모형분석표명,여휴대CC기인형적란소암환자상비,휴대TT기인형환자적PFS(분별위21.1、8.6개월;HR =2.19,95％ CI위1.14 ～4.22,P=0.009)화OS(분별위28.5、19.3개월;HR =2.22,95％ CI위1.06 ～4.64,P =0.021)균명현축단.이령외5개tagSNP(즉rs3212986、rs735482、rs3212955、rs12610134、rs3212958)위점적기인형분포여란소암환자적화료민감성급예후균무관(P＞0.05).결론ERCC1기인rs11615위점적SNP가능성위예측란소암환자박류약물화료민감성급예후적분자표지물
Objective To explore the relationship among single nucleotide polymorphism (SNP) of excision repair cross-complementing 1 (ERCC1) gene,chemotherapy sensitivity and clinical outcomes of epithelial ovarian cancer (EOC) patients treated with platinum.Methods Six tag single nucleotide polymorphisms (tagSNP;rs11615,rs3212986,rs735482,rs3212955,rs12610134 and rs3212958) were chose from ERCC1 gene.The genotypes of 6 tagSNP were determined by Snapshot method in 220 EOC patients.Primary clinical outcomes parameter contained EOC patients'responses to platinum-based chemotherapy,progression-free survival (PFS) and overall survival (OS) were analysed.Results The rs11615 C/T SNP of ERCC1,CC,CT and TT genotype frequencies were 53.1％,45.6％,1.4％ in responders to platinum-based chemotherapy,while 52.0％,35.6％,12.3％ in non-responders,respectively,in which there was significant difference between the two groups(P =0.002).Compared with the patients with CC genotype,the patients carrying TT genotype had a significantly poor response to platinum-based chemotherapy (OR =6.22,95％ CI:1.12-34.42).Similarly,the genotypes frequencies distribution of rs11615 C/T SNP of ERCC1 was different between the recurrence and non-recurrence group,death and survival group (all P ＜ 0.05).Kaplan-Meier survival analysis showed that the genotypes frequencies distribution of rs11615 C/T SNP of ERCC1 was associated with PFS and OS(P ＜ 0.01) of EOC patients.Cox's multivariate analysis suggested that patients with TT genotype had a shorter PFS (HR =2.19,95 ％ CI:1.14-4.22,P =0.009) and OS (HR =2.22,95 ％ CI:1.06-4.64,P =0.021) compared with those carrying CC genotype [adjusting for age,International Federation of Gynecology and Obstetrics (FIGO) stage,pathological type,grade and tumor residual size].The genotypes frequencies distribution of rs3212986,rs735482,rs3212955,rs12610134 and rs3212958 SNP of ERCC1 did not show the significant difference between the responders to platinum-based chemotherapy and non-responders.The other 5 tagSNP may not be associated with the PFS and OS of EOC patients (all P ＞ 0.05).Conclusion The rs 11615 SNP of ERCC1 may become a valuable prognostic biomarker for EOC patients treated with platinum-based chemotherapy.
