Dataset Information

Systematic analysis of mRNA expression profiles in NSCLC cell lines to screen metastasis-related genes.

ABSTRACT: Lung cancer is the most prevalent cancer in humans and has the lowest survival outcomes due to its high metastatic potential. The aim of the present study was to screen for metastasis?related genes (MRGs) by investigating the differential expression genes (DEGs) identified by the mRNA expression profiles in SPC?A?1sci (highly metastatic) and SPC-A-1 (parental) cells. DEGs were screened using Genespring software. Gene Ontology and pathway enrichment analyses of these DEGs were performed. Interaction networks between the proteins encoded by the DEGs were identified using the database BioGRID and were visualized by Cytoscape. Modular analysis of the protein?protein interaction network was performed in CFinder. Among these DEGs, the expression levels of 18 genes were examined in SPC?A?1sci and SPC?A?1 cell lines with reverse transcription?quantitative polymerase chain reaction, and 10 of the 18 genes were assessed by western blotting to validate the results of the microarray. Furthermore, the role of metallothionein 1X (MT1X) in non?small cell lung cancer was explored in functional assays and 72 pairs of clinical samples in vitro. Finally, 4,838 DEGs were screened, including 798 upregulated and 4,040 downregulated genes. The significantly enriched functions included gene expression, cytosol and poly?(A) RNA binding, and the most enriched pathway was biosynthesis of antibiotics. Furthermore, MT1X was revealed to promote the migration and invasion ability in SPC?A?1sci and PC?9 lung cancer cell lines. Therefore, MT1X was identified as a candidate MRG through systematic analysis in the present microarray, which was demonstrated to offer potential reference value in screening MRGs.

SUBMITTER: Liu Y

PROVIDER: S-EPMC5355670 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Systematic analysis of mRNA expression profiles in NSCLC cell lines to screen metastasis-related genes.

Liu Ying Y Liu Lei L Yu Tao T Lin He-Chun HC Chu Dandan D Deng Wei W Yan Ming-Xia MX Li Jing J Yao Ming M

Molecular medicine reports 20161101 6

Lung cancer is the most prevalent cancer in humans and has the lowest survival outcomes due to its high metastatic potential. The aim of the present study was to screen for metastasis‑related genes (MRGs) by investigating the differential expression genes (DEGs) identified by the mRNA expression profiles in SPC‑A‑1sci (highly metastatic) and SPC-A-1 (parental) cells. DEGs were screened using Genespring software. Gene Ontology and pathway enrichment analyses of these DEGs were performed. Interact ...[more]

PMID: 27840927

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Project description:Breast cancer researchers use cell lines to model myriad phenomena ranging from DNA repair to cancer stem cell phenotypes. Though appropriate, and even requisite, for many studies, the suitability of cell lines as tumour models has come into question owing to possibilities of tissue culture artefacts and clonal selection. These issues are compounded by the inability of cancer cells grown in isolation to fully model the in situ tumour environment, which also contains a plethora of non-tumour cell types. It is thus important to understand similarities and differences between cancer cell lines and the tumours that they represent so that the optimal tumour models can be chosen to answer specific research questions.In the present study, we compared the RNA-sequencing transcriptomes of a collection of breast cancer cell lines to transcriptomes obtained from hundreds of tumours using The Cancer Genome Atlas. Tumour purity was accounted for by analysis of stromal and immune scores using the ESTIMATE algorithm so that differences likely resulting from non-tumour cells could be accounted for.We found the transcriptional characteristics of breast cancer cell lines to mirror those of the tumours. We identified basal and luminal cell lines that are most transcriptionally similar to their respective breast tumours. Our comparison of expression profiles revealed pronounced differences between breast cancer cell lines and tumours, which could largely be attributed to the absence of stromal and immune components in cell culture. A focus on the Wnt pathway revealed the transcriptional downregulation or absence of several secreted Wnt antagonists in culture. Gene set enrichment analysis suggests that cancer cell lines have enhanced proliferation and glycolysis independent of stromal and immune contributions compared with breast cancer cells in situ.This study demonstrates that many of the differences between breast cancer cell lines and tumours are due to the absence of stromal and immune components in vitro. Hence, extra precautions should be taken when modelling extracellular proteins in vitro. The specific differences discovered emphasize the importance of choosing an appropriate model for each research question.

Dataset Information

Systematic analysis of mRNA expression profiles in NSCLC cell lines to screen metastasis-related genes.

Publications

Systematic analysis of mRNA expression profiles in NSCLC cell lines to screen metastasis-related genes.

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