Microarray expression profile analysis of long non-coding RNAs of advanced stage human gastric cardia adenocarcinoma

Mol Genet Genomics. 2014 Jun;289(3):291-302. doi: 10.1007/s00438-013-0810-4. Epub 2014 Jan 12.

Abstract

Gastric cardia adenocarcinoma (GCA) is a unique malignant tumor for its characteristics different from gastric and esophageal cancer epidemiologically and pathologically. The incidence of GCA has steadily increased for the last three decades and many patients are diagnosed with advanced stage because of the lack of typical and obvious symptoms at an early stage. To gain insight into the molecular mechanisms of GCA of advanced stage, we investigated the microarray expression profile of long non-coding RNAs of 12 advanced stage GCA patients. Long non-coding RNAs (lncRNAs) lack protein-coding potential and are over 200 bp in length. LncRNAs are known to be involved in the multifactor and multistep processes of tumor development and metastasis. In this study, we performed lncRNA transcriptome profiling of GCA biopsy tissue from 12 GCA patients who were confirmed by pathology to have developed lymph node metastasis and 12 paired non-cancerous gastric cardia tissues to determine if a gene expression profile unique to the lymph node metastasis group could be detected. Comparison of differentially expressed transcripts between the groups identified eight pathways that corresponded to down-regulated transcripts and 18 pathways that corresponded to up-regulated transcripts (p value cut-off 0.05). Gene ontology analysis showed that the up-regulated transcripts were most highly enriched in SRP-dependent cotranslational protein targeting to membrane, cytosolic ribosome, and structural constituent of ribosome, and the down-regulated transcripts were highly enriched in carboxylic acid transport, focal adhesion, and cation binding. This study shows that lncRNAs dysregulation exerts important roles in human GCA lymph node metastasis, indicating that lncRNAs are novel candidate biomarkers for the clinical diagnosis of advanced stage GCA and that could be targets for further therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Aged
  • Cluster Analysis
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Annotation
  • Neoplasm Staging
  • RNA, Long Noncoding / genetics*
  • RNA, Messenger / genetics
  • Reproducibility of Results
  • Signal Transduction
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*

Substances

  • H19 long non-coding RNA
  • RNA, Long Noncoding
  • RNA, Messenger