Dataset Information

MicroRNA signature characterizes primary tumors that metastasize in an esophageal adenocarcinoma rat model.

ABSTRACT:

Objective

To establish a miRNA signature for metastasis in an animal model of esophageal adenocarcinoma (EAC).

Background

The incidence of esophageal adenocarcinoma (EAC) has dramatically increased and esophageal cancer is now the sixth leading cause of cancer deaths worldwide. Mortality rates remain high among patients with advanced stage disease and esophagectomy is associated with high complication rates. Hence, early identification of potentially metastatic disease would better guide treatment strategies.

Methods

The modified Levrat's surgery was performed to induce EAC in Sprague-Dawley rats. Primary EAC and distant metastatic sites were confirmed via histology and immunofluorescence. miRNA profiling was performed on primary tumors with or without metastasis. A unique subset of miRNAs expressed in primary tumors and metastases was identified with Ingenuity Pathway Analysis (IPA) along with upstream and downstream targets. miRNA-linked gene expression analysis was performed on a secondary cohort of metastasis positive (n=5) and metastasis negative (n=28) primary tumors.

Results

The epithelial origin of distant metastasis was established by IF using villin (VIL1) and mucin 5AC (MUC5AC) antibodies. miRNome analysis identified four down-regulated miRNAs in metastasis positive primary tumors compared to metastasis negative tumors: miR-92a-3p (p=0.0001), miR-141-3p (p=0.0022), miR-451-1a (p=0.0181) and miR133a-3p (p=0.0304). Six target genes identified in the top scoring networks by IPA were validated as significantly, differentially expressed in metastasis positive primary tumors: Ago2, Akt1, Kras, Bcl2L11, CDKN1B and Zeb2.

Conclusion

In vivo metastasis was confirmed in the modified Levrat's model. Analysis of the primary tumor identified a distinctive miRNA signature for primary tumors that metastasized.

SUBMITTER: Zaidi AH

PROVIDER: S-EPMC4380408 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

MicroRNA signature characterizes primary tumors that metastasize in an esophageal adenocarcinoma rat model.

Zaidi Ali H AH Saldin Lindsey T LT Kelly Lori A LA Bergal Linda L Londono Ricardo R Kosovec Juliann E JE Komatsu Yoshihiro Y Kasi Pashtoon M PM Shetty Amit A AA Keane Timothy J TJ Thakkar Shyam J SJ Huleihel Luai L Landreneau Rodney J RJ Badylak Stephen F SF Jobe Blair A BA

PloS one 20150331 3

<h4>Objective</h4>To establish a miRNA signature for metastasis in an animal model of esophageal adenocarcinoma (EAC).<h4>Background</h4>The incidence of esophageal adenocarcinoma (EAC) has dramatically increased and esophageal cancer is now the sixth leading cause of cancer deaths worldwide. Mortality rates remain high among patients with advanced stage disease and esophagectomy is associated with high complication rates. Hence, early identification of potentially metastatic disease would bette ...[more]

PMID: 25826212

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Dataset Information

MicroRNA signature characterizes primary tumors that metastasize in an esophageal adenocarcinoma rat model.

Objective

Background

Methods

Results

Conclusion

Publications

MicroRNA signature characterizes primary tumors that metastasize in an esophageal adenocarcinoma rat model.

Similar Datasets

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