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

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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.

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Abbreviations

lncRNA:

Long non-coding RNA

GCA:

Gastric cardia adenocarcinoma

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China No. 81301763 and No. 30670956.

Conflict of interest

The authors have no conflicts of interest to declare.

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Authors and Affiliations

  1. Oncology Department of the First Affiliated Hospital of Henan University of Science and Technology, No. 24 Jinghua Road, Luoyang, Henan, China

    Ying Wang, Xiaoshan Feng, Ruinuo Jia, Gang Liu, Mengxi Zhang & Shegan Gao

  2. State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 Changlexi Road, Xi’an, Shaanxi, China

    Daiming Fan

Authors
  1. Ying Wang
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Corresponding authors

Correspondence to Daiming Fan or Shegan Gao.

Additional information

Communicated by S. Hohmann.

Y. Wang and X. Feng contributed equally to this work.

Transcript profiling: Arraystar website: Human LncRNA Microarray V2.0. http://www.arraystar.com/manage/UploadFile/201132132855779.pdf.

Electronic supplementary material

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438_2013_810_MOESM1_ESM.tif

LncRNA expression profiles displayed in (a) Volcano plots and (b) a scatter plot. Volcano plots were used to visualize the differential expression between tumor and normal tissues and were constructed using fold-change values and p values. The vertical lines correspond to twofold up- and down-regulation and the horizontal line represents a p value of 0.05. The red point represents the statistically significant differentially expressed lncRNAs. The scatterplot was used to assess the variation (or reproducibility) between microarray chips. (c) Analysis of 12 pairs of lncRNA chips using a boxplot. The boxplot was used to compare the distributions of expression values for the tumor and normal tissues samples after normalization (TIFF 708 kb)

438_2013_810_MOESM2_ESM.tif

mRNA expression profiles displayed in (a) Volcano plots and (b) a scatter plot. Volcano plots were used to visualize the differential expression between tumor and normal tissues and were constructed using fold-change values and p values. The vertical lines correspond to twofold up- and down-regulation and the horizontal line represents a p value of 0.05. The red point represents the statistically significant differentially expressed mRNAs. The scatterplot was used to assess the variation (or reproducibility) between microarray chips. (c) Analysis of 12 pairs of mRNA chips using a boxplot. The meaning of boxplot is as aforementioned in S.Fig 1 (TIFF 1005 kb)

438_2013_810_MOESM3_ESM.xlsx

Online Resource 1. Primers used for quantitative real-time PCR (qRT-PCR) to validate the expression of 12 lncRNAs (XLSX 12 kb)

438_2013_810_MOESM4_ESM.xlsx

Online Resource 2. The lncRNA expression profiling data from the microarray analysis of GCA tissue samples (XLSX 13847 kb)

438_2013_810_MOESM5_ESM.xls

Online Resource 3. The consistently up-regulated and down-regulated lncRNAs between GCA tumor and normal tissues (XLS 2491 kb)

438_2013_810_MOESM6_ESM.xlsx

Online Resource 4. The mRNA expression profiling data from the microarray analysis of GCA tissue samples (XLSX 11460 kb)

438_2013_810_MOESM7_ESM.xls

Online Resource 5. The consistently up-regulated and down-regulated mRNAs between GCA tumor and normal tissues (XLS 2324 kb)

Online Resource 6. Gene Ontology (GO) analysis of the transcripts (XLSX 215 kb)

Online Resource 7. Pathway analysis of the transcripts (XLSX 29 kb)

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Wang, Y., Feng, X., Jia, R. et al. Microarray expression profile analysis of long non-coding RNAs of advanced stage human gastric cardia adenocarcinoma. Mol Genet Genomics 289, 291–302 (2014). https://doi.org/10.1007/s00438-013-0810-4

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  • DOI: https://doi.org/10.1007/s00438-013-0810-4

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