Gastric adenocarcinoma has a unique microRNA signature not present in esophageal adenocarcinoma

Zheng Chen, Rama Saad, Peilin Jia, Dunfa Peng, Shoumin Zhu, M. Kay Washington, Zhongming Zhao, Zekuan Xu, Wael El-Rifai

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

BACKGROUND MicroRNAs (miRNAs) play critical roles in tumor development and progression. The finding that a single miRNA can regulate hundreds of genes places miRNAs at critical hubs of signaling pathways. For the current study, the authors investigated the miRNA expression profile of gastric adenocarcinomas and compared it with esophageal adenocarcinomas to better identify a unique miRNA signature of gastric adenocarcinoma. METHODS miRNA expression profiles were obtained using 2 different proprietary microarray platforms on primary gastric adenocarcinoma tissue samples. The cross comparison of results identified 17 up-regulated miRNAs and 12 down-regulated miRNAs that overlapped in both platforms. Quantitative real-time polymerase chain reaction was performed for independent validation of a representative set of 8 miRNAs in gastric and esophageal adenocarcinomas compared with normal gastric mucosa or esophageal mucosa, respectively. RESULTS The deregulation of miR-146b-5p, miR-375, miR-148a, miR-31, and miR-451 was associated significantly with gastric adenocarcinomas. Conversely, deregulation of miR-21 (up-regulation) and miR-133b (down-regulation) was detectable in both gastric and esophageal adenocarcinomas. It was noteworthy that miR-200a was significantly down-regulated in gastric adenocarcinoma samples (P =.04) but was up-regulated in esophageal adenocarcinoma samples (P =.001). In addition, the expression level of miR-146b-5p displayed a strong correlation with the tumor stage of gastric cancer. CONCLUSIONS Gastric adenocarcinoma displayed a unique miRNA signature that distinguished it from esophageal adenocarcinoma. This specific signature may reflect differences in the etiology and/or molecular signaling in these 2 closely related cancers. The current findings suggest important miRNA candidates that can be investigated for their biological functions and for their possible diagnostic, prognostic, and therapeutic role in gastric adenocarcinoma.

Original languageEnglish (US)
Pages (from-to)1985-1993
Number of pages9
JournalCancer
Volume119
Issue number11
DOIs
StatePublished - Jun 1 2013
Externally publishedYes

Fingerprint

MicroRNAs
Stomach
Adenocarcinoma
Neoplasms
Gastric Mucosa
Stomach Neoplasms
Real-Time Polymerase Chain Reaction
Up-Regulation
Down-Regulation

Keywords

  • esophageal adenocarcinoma
  • gastric adenocarcinoma
  • microarray
  • microRNA
  • prognosis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Gastric adenocarcinoma has a unique microRNA signature not present in esophageal adenocarcinoma. / Chen, Zheng; Saad, Rama; Jia, Peilin; Peng, Dunfa; Zhu, Shoumin; Washington, M. Kay; Zhao, Zhongming; Xu, Zekuan; El-Rifai, Wael.

In: Cancer, Vol. 119, No. 11, 01.06.2013, p. 1985-1993.

Research output: Contribution to journalArticle

Chen, Z, Saad, R, Jia, P, Peng, D, Zhu, S, Washington, MK, Zhao, Z, Xu, Z & El-Rifai, W 2013, 'Gastric adenocarcinoma has a unique microRNA signature not present in esophageal adenocarcinoma', Cancer, vol. 119, no. 11, pp. 1985-1993. https://doi.org/10.1002/cncr.28002
Chen, Zheng ; Saad, Rama ; Jia, Peilin ; Peng, Dunfa ; Zhu, Shoumin ; Washington, M. Kay ; Zhao, Zhongming ; Xu, Zekuan ; El-Rifai, Wael. / Gastric adenocarcinoma has a unique microRNA signature not present in esophageal adenocarcinoma. In: Cancer. 2013 ; Vol. 119, No. 11. pp. 1985-1993.
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AU - Chen, Zheng

AU - Saad, Rama

AU - Jia, Peilin

AU - Peng, Dunfa

AU - Zhu, Shoumin

AU - Washington, M. Kay

AU - Zhao, Zhongming

AU - Xu, Zekuan

AU - El-Rifai, Wael

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N2 - BACKGROUND MicroRNAs (miRNAs) play critical roles in tumor development and progression. The finding that a single miRNA can regulate hundreds of genes places miRNAs at critical hubs of signaling pathways. For the current study, the authors investigated the miRNA expression profile of gastric adenocarcinomas and compared it with esophageal adenocarcinomas to better identify a unique miRNA signature of gastric adenocarcinoma. METHODS miRNA expression profiles were obtained using 2 different proprietary microarray platforms on primary gastric adenocarcinoma tissue samples. The cross comparison of results identified 17 up-regulated miRNAs and 12 down-regulated miRNAs that overlapped in both platforms. Quantitative real-time polymerase chain reaction was performed for independent validation of a representative set of 8 miRNAs in gastric and esophageal adenocarcinomas compared with normal gastric mucosa or esophageal mucosa, respectively. RESULTS The deregulation of miR-146b-5p, miR-375, miR-148a, miR-31, and miR-451 was associated significantly with gastric adenocarcinomas. Conversely, deregulation of miR-21 (up-regulation) and miR-133b (down-regulation) was detectable in both gastric and esophageal adenocarcinomas. It was noteworthy that miR-200a was significantly down-regulated in gastric adenocarcinoma samples (P =.04) but was up-regulated in esophageal adenocarcinoma samples (P =.001). In addition, the expression level of miR-146b-5p displayed a strong correlation with the tumor stage of gastric cancer. CONCLUSIONS Gastric adenocarcinoma displayed a unique miRNA signature that distinguished it from esophageal adenocarcinoma. This specific signature may reflect differences in the etiology and/or molecular signaling in these 2 closely related cancers. The current findings suggest important miRNA candidates that can be investigated for their biological functions and for their possible diagnostic, prognostic, and therapeutic role in gastric adenocarcinoma.

AB - BACKGROUND MicroRNAs (miRNAs) play critical roles in tumor development and progression. The finding that a single miRNA can regulate hundreds of genes places miRNAs at critical hubs of signaling pathways. For the current study, the authors investigated the miRNA expression profile of gastric adenocarcinomas and compared it with esophageal adenocarcinomas to better identify a unique miRNA signature of gastric adenocarcinoma. METHODS miRNA expression profiles were obtained using 2 different proprietary microarray platforms on primary gastric adenocarcinoma tissue samples. The cross comparison of results identified 17 up-regulated miRNAs and 12 down-regulated miRNAs that overlapped in both platforms. Quantitative real-time polymerase chain reaction was performed for independent validation of a representative set of 8 miRNAs in gastric and esophageal adenocarcinomas compared with normal gastric mucosa or esophageal mucosa, respectively. RESULTS The deregulation of miR-146b-5p, miR-375, miR-148a, miR-31, and miR-451 was associated significantly with gastric adenocarcinomas. Conversely, deregulation of miR-21 (up-regulation) and miR-133b (down-regulation) was detectable in both gastric and esophageal adenocarcinomas. It was noteworthy that miR-200a was significantly down-regulated in gastric adenocarcinoma samples (P =.04) but was up-regulated in esophageal adenocarcinoma samples (P =.001). In addition, the expression level of miR-146b-5p displayed a strong correlation with the tumor stage of gastric cancer. CONCLUSIONS Gastric adenocarcinoma displayed a unique miRNA signature that distinguished it from esophageal adenocarcinoma. This specific signature may reflect differences in the etiology and/or molecular signaling in these 2 closely related cancers. The current findings suggest important miRNA candidates that can be investigated for their biological functions and for their possible diagnostic, prognostic, and therapeutic role in gastric adenocarcinoma.

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