The microRNAs, MiR-31 and MiR-375, as candidate markers in Barrett's esophageal carcinogenesis.
The microRNAs, MiR-31 and MiR-375, as candidate markers in Barrett's esophageal carcinogenesis.
复制标题
DOI：
10.1002/gcc.21934
复制
发表时间：
2012-05
影响因子：
3.7
通讯作者：
Guda, Kishore
中科院分区：
文献类型：
--
作者：
Leidner, Rom S.;Ravi, Lakshmeswari;Leahy, Patrick;Chen, Yanwen;Bednarchik, Beth;Streppel, Mirte;Canto, Marcia;Wang, Jean S.;Maitra, Anirban;Willis, Joseph;Markowitz, Sanford D.;Barnholtz-Sloan, Jill;Adams, Mark D.;Chak, Amitabh;Guda, Kishore
目前迫切需要鉴定能够可靠地帮助对Barrett食管患者的食管腺癌（EAC）风险进行分层的分子标志物。MicroRNA（miRNA/miR）是一类生物分子。在目前的横断面研究中，我们描述了肿瘤发展进行性阶段的miRNA改变，即，因此，本研究旨在鉴定与化生-异型增生-腺癌潜在相关的候选miRNA。使用下一代测序（NGS）作为不可知发现平台，然后在总共20个EAC中进行定量实时PCR（qPCR）验证，我们鉴定了26种与配对正常食管鳞状（nSQ）组织相比在EAC中高度和频繁失调的miRNA（>50%的病例中≥4倍）。然后，我们通过qPCR评估了Barrett化生（BM）/nSQ（n = 15）和高度异型增生（HGD）/nSQ（n = 14）的激光显微切割活检对中的26种EAC衍生的miRNA，以绘制从BM到HGD和到EAC进展期间的失调时间。我们发现26个候选miRNAs中有23个在最早的阶段BM被解除调节，因此作为进展的分子标记物没有信息。然而，两种miRNAs，miR-31和-31*，仅在HGD和EAC病例中显示频繁下调，表明与从BM向HGD的转变相关。第三种miRNA，miR-375，仅在EAC中显示出显著的下调，而在BM或HGD病变中均未显示，表明其与浸润性癌的进展相关。综上所述，我们提出miR-31和-375作为新的候选microRNA，分别与Barrett食管的早期和晚期恶性进展特异性相关。
There is a critical need to identify molecular markers that can reliably aid in stratifying esophageal adenocarcinoma (EAC) risk in patients with Barrett's esophagus. MicroRNAs (miRNA/miR) are one such class of biomolecules. In the present cross-sectional study, we characterized miRNA alterations in progressive stages of neoplastic development, i.e., metaplasia–dysplasia–adenocarcinoma, with an aim to identify candidate miRNAs potentially associated with progression. Using next generation sequencing (NGS) as an agnostic discovery platform, followed by quantitative real-time PCR (qPCR) validation in a total of 20 EACs, we identified 26 miRNAs that are highly and frequently deregulated in EACs (≥4-fold in >50% of cases) when compared to paired normal esophageal squamous (nSQ) tissue. We then assessed the 26 EAC-derived miRNAs in laser microdissected biopsy pairs of Barrett's metaplasia (BM)/nSQ (n = 15), and high-grade dysplasia (HGD)/nSQ (n = 14) by qPCR, to map the timing of deregulation during progression from BM to HGD and to EAC. We found that 23 of the 26 candidate miRNAs were deregulated at the earliest step, BM, and therefore noninformative as molecular markers of progression. Two miRNAs, miR-31 and –31*, however, showed frequent downregulation only in HGD and EAC cases suggesting association with transition from BM to HGD. A third miRNA, miR-375, showed marked downregulation exclusively in EACs and in none of the BM or HGD lesions, suggesting its association with progression to invasive carcinoma. Taken together, we propose miR-31 and –375 as novel candidate microRNAs specifically associated with early- and late-stage malignant progression, respectively, in Barrett's esophagus.
登录
查看更多内容
影响因子：
9.8
作者：
Prasad, Ganapathy A.;Bansal, Ajay;Sharma, Prateek;Wang, Kenneth K.
通讯作者：
Wang, Kenneth K.
影响因子：
3.1
作者：
Li, Xiaoli;Lin, Rui;Li, Jiansheng
通讯作者：
Li, Jiansheng
影响因子：
9.6
作者：
Wijnhoven, B. P. L.;Hussey, D. J.;Michael, M. Z.
通讯作者：
Michael, M. Z.
影响因子：
9.8
作者：
Bansal, Ajay;Lee, I. H.;Christenson, L. K.
通讯作者：
Christenson, L. K.
影响因子：
11.2
作者：
Creighton CJ;Fountain MD;Yu Z;Nagaraja AK;Zhu H;Khan M;Olokpa E;Zariff A;Gunaratne PH;Matzuk MM;Anderson ML
通讯作者：
Anderson ML