摘要
目的探讨微小RNA-21（miR-21）在胃癌组织中表达的意义，并评估miR-21与含奥沙利铂的二药联合方案治疗晚期胃癌患者临床预后的相关性。方法入组患者均为不能手术或手术后复发的转移性胃癌。化疗方案为奥沙利铂联合替吉奥（S-1）或奥沙利铂联合去氧氟脲苷。从52例福马林固定后白蜡包埋（FFPE）的胃癌组织样本中筛选鉴定出可以作为预后标志物的miRNA。从胃癌患者FFPE肿瘤组织样本和正常胃组织中分别提取出总RNA，应用荧光定量聚合酶链反应（FQ—PCR）定量分析miRNA（包括let-7g、miR-200c、miR-140、miR-21、miR-192、miR-181b）表达水平，并分析其与胃癌患者预后的相关性。结果胃癌组织中miR-21表达水平显著高于正常胃组织（5．43±7．95比1．00）。多因素生存分析显示：miR．21高表达胃癌患者总生存期显著低于miR-21低表达患者，中位生存期分别为5．03（2．67～7．40）和8．74（6．58～10．89）个月，与miR-21低表达胃癌患者比较，其死亡风险比（HR）为8．11[95％可信区间（CI）：2．47～26．59，P〈0．01]；2个疗程后疗效较好者生存期显著高于疗效较差者，疗效为部分缓解（PR）、稳定（sD）、进展（PD）的患者中位生存期分别为8．41（5．29～11．52）、10．57（5．68～15．47）和5．10（3．11～7．08）个月。相对于PR患者，SD、PD患者的HR分别为0．96（95％C1：0．36～2．54，P〉0．05）和6．65（95％CI：2．08～21．24，P〈0．01）。结论胃癌组织中存在微小RNA异常表达，其中miR-21高表达与晚期胃癌不良预后显著相关。
] Objective To investigate the significance of microRNA-21 （ miRNA-21 ,miR-21 ） ex- pression in gastric cancer and assess the correlation between miRNA-21 and clinical outcome of the late- stage gastric cancer patients treated with chemotherapy of allied two medicines containing Oxaliplatin. Methods Metastatic gastric cancer patients who are not candidates for curative surgery or recurred after operation were recruited for the trial. The patients were treated with S-1 plus i. v. with Oxaliplatin or Doxi- fluridine plus i. v. with Oxaliplatin. The expression of candidate miRNAs was quantified from fifty-two late stage gastric cancer formalin fixed paraffin-embedded （FFPE） specimens. Total RNAs were extracted from normal and gastric tumor specimens. The levels of miRNAs （ including let-Tg, miR-200c, miR-140, miR-21, miR-192 and miR-181 b） were quantified using real time fluorescent quantitative polymerase chain reaction （FQ-PCR） expression analysis. In addition,we will further analyze its clinical significance in gastric canc- er. Results The expression of miR-21 was significantly overexpressed in gastric tumors compared to normal gastric tissues （5.43 ＋7.95 vs 1.00）. Kaplan-Meier survival analysis revealed that high level of miR-21 expression was closely associated with poor oerall survival （OS） for Oxaliplatin based regimens. The medi- an OS of miR-2i low expression patient subgroup was 8.74 （6. 58-10. 89 ） months, while was only 5.03 （2. 67-7.40 ） months for the high expression subgroup, patients with high miR-21 expression showed a sig- nificant increase in hazard ratio （HR） for death [ HR = 8. 11,95% confidence interval （CI） ：2.47-26. 59, P 〈 0. 01 ]. The efficacy after two cycles was also found to be significant variable in predicting OS ,the medi- an OS for patients with patial response （ PR）, stable disease （SD） and progressive diease （PD） were 8.41（5.29-11.52）, 10. 57 （ 5.68-15.47 ） and 5. 10 （ 3.11-7.08 ） months respectively. Compared to patients with PR,the HR for death were 0. 96 （95% CI：O. 36-2. 54, P 〉0. 05） and 6. 65 （95% CI：2. 08-21.24, P 〈 0. 01 ） for patients with SD and PD. Conclusion Abnormal versions of mieroRNAs have been impli- cated in gastric cancer, and miR-21 holds great potential as prognostic biomarkers in late stage gastric cancer.
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2013年第2期252-255,共4页
Chinese Journal of Experimental Surgery
基金
同家自然科学基金资助项目（81171653、30972703）
江苏省自然科学基金资助项目（BK2011246、BK2011247）
常州市社会发展计划基金资助项目（CE20125017、CJ20112020、CZ20110024、CS20102020）
常州市科技支撑计划资助项目（CE20125017）
常州市国际科技合作项目（CZ20110024）
