MicroRNAs as a potential prognostic factor in gastric cancer

MicroRNAs as a potential prognostic factor in gastric cancer
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DOI:
10.3748/wjg.v17.i35.3976
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发表时间:
2011-09-21
影响因子:
4.3
通讯作者:
Kushnir, Michal
Kushnir, Michal
中科院分区:
医学2区
文献类型:
--
作者:
Brenner, Baruch;Hoshen, Moshe B.;Kushnir, Michal

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目的:比较复发性和非复发性胃癌患者原发肿瘤中的microRNA(miR)谱:研究组包括45例1995年至2005年接受根治性胃切除术且无辅助或新辅助治疗且有足够肿瘤内容的患者。从福尔马林固定的石蜡包埋的肿瘤样品中提取总RNA,保留小RNA部分。使用miR微阵列进行初始分析,以识别切除后复发的潜在生物标志物。随后通过定量实时聚合酶链反应(qRT-PCR)验证差异miR的表达。比较了术后36个月内复发的患者的结果(预后不良组,n = 14,31%)和那些没有预后良好组31例,占69%。三种miR,miR-451,发现miR-199 a-3 p和miR-195在预后良好的患者与预后不良的患者的肿瘤中差异表达(P分别< 0.0002、0.0027和0.0046)。每种miR的高表达与复发和生存的预后较差相关。使用miR-451,无复发的阳性预测值为100%(13/13)。qRT-PCR验证差异miR的表达,显示与微阵列数据高度相关,并相似地分离到预后groups.CONCLUSION:本研究确定了3个miR,miR-451,miR-199 a-3 p和miR-195可预测胃癌复发。其中,miR-451具有最强的预后影响。
AIM: To compare the microRNA (miR) profiles in the primary tumor of patients with recurrent and non-recurrent gastric cancer.METHODS: The study group included 45 patients who underwent curative gastrectomies from 1995 to 2005 without adjuvant or neoadjuvant therapy and for whom adequate tumor content was available. Total RNA was extracted from formalin-fixed paraffin-embedded tumor samples, preserving the small RNA fraction. Initial profiling using miR microarrays was performed to identify potential biomarkers of recurrence after resection. The expression of the differential miRs was later verified by quantitative real-time polymerase chain reaction (qRT-PCR). Findings were compared between patients who had a recurrence within 36 mo of surgery (bad-prognosis group, n = 14, 31%) and those who did not (good-prognosis group, n = 31, 69%).RESULTS: Three miRs, miR-451, miR-199a-3p and miR-195 were found to be differentially expressed in tumors from patients with good prognosis vs patients with bad prognosis (P < 0.0002, 0.0027 and 0.0046 respectively). High expression of each miR was associated with poorer prognosis for both recurrence and survival. Using miR-451, the positive predictive value for non-recurrence was 100% (13/13). The expression of the differential miRs was verified by qRT-PCR, showing high correlation to the microarray data and similar separation into prognosis groups.CONCLUSION: This study identified three miRs, miR-451, miR-199a-3p and miR-195 to be predictive of recurrence of gastric cancer. Of these, miR-451 had the strongest prognostic impact.