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Transcriptome analysis of non-small cell lung cancer and genetically matched adjacent normal tissues identifies novel prognostic marker genes

Genes & Genomics volume 39, pages277–284(2017)Cite this article

Abstract

Lung cancer can be classified into two different types, non-small cell lung cancer (NSCLC) and small cell lung cancer. Up to 85% of lung cancer cases are NSCLC. To identify prognostic marker genes for NSCLC, we conducted 10 pairs of genetically matched transcriptome (NSCLC and adjacent normal tissues obtained from 10 patients) analysis using next-generation sequencing. Pathway analysis revealed that the genes associated with the cell cycle are highly upregulated in NSCLC. Integrative analysis of two independent NSCLC studies, 71 pairs (GSE40419) and 58 pairs (TCGA-LUAD), also confirmed that cell cycle–related genes are mostly upregulated in NSCLC. All three independent NSCLC transcriptomes concordantly identified 10 potential tumor-marker genes that are highly expressed as well as significantly altered in NSCLC. A quantitative real-time polymerase chain reaction experiment validated the altered expressions of the genes. Among them, downregulation of MFAP4 and AGER and upregulation of SPP1 genes in NSCLC compared to normal tissues were significantly associated with poor prognosis as evaluated by Kaplan–Meier survival and receiver operating characteristic analyses. A further analysis indicated that the expression ratio of MFAP4 and SPP1 or AGER and SPP1 can be used as potential prognostic marker genes for NSCLC.

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Abbreviations

NSCLC:

Non-small cell lung cancer

NGS:

Next-generation sequencing

TCGA:

The cancer genome atlas

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Acknowledgements

This study is supported by the R&D program of MKE/KEIT (10040393, Development and commercialization of molecular diagnostic technologies for lung cancer through clinical validation). The biospecimens and data used for this study were provided by the Biobank of Chungnam University Hospital, Kyungpook National University Hospital, and Keimyung Human Bio-Resource Bank (KHBB), a member of the National Biobank of Korea, which is supported by the Ministry of Health and Welfare. All samples derived from the National Biobank of Korea were obtained with informed consent under institutional review board–approved protocols.

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Affiliations

  1. Department of Medical Laser, Graduate School, Dankook University, Dongnam-gu, Cheonan, 31116, Republic of Korea
    • Man Seok Bang
    • , Jung-ju Lee
    • , Yea-Jin Lee
    •  & Chung-Hun Oh
  2. Department of Oral Physiology, College of Dentistry, Dankook University, Cheonan, 31116, Republic of Korea
    • Chung-Hun Oh
  3. Department of Microbiology, College of Natural Sciences, Dankook University, Cheonan, 31116, Republic of Korea
    • Keunsoo Kang
  4. Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
    • Jin Eun Choi
  5. Department of Dental Pharmacology, School of Dentistry, Dankook University, Cheonan, 31116, Republic of Korea
    • Ju Yeon Ban
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Correspondence to Chung-Hun Oh.

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Conflicts of interest

The authors declare that they have no conflict of interest. Man Seok Bang declares that he has no conflict of interest. Keunsoo Kang declares that he has no conflict of interest. Jung-ju Lee declares that she has no conflict of interest. Yea-Jin Lee Lee declares that she has no conflict of interest. Jin Eun Choi declares that she has no conflict of interest. Ju Yeon Ban declares that she has no conflict of interest. Chung-Hun Oh declares that he has no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Man Seok Bang and Keunsoo Kang are the co-first authors.

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Bang, M.S., Kang, K., Lee, J. et al. Transcriptome analysis of non-small cell lung cancer and genetically matched adjacent normal tissues identifies novel prognostic marker genes. Genes Genom 39, 277–284 (2017). https://doi.org/10.1007/s13258-016-0492-5

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Keywords

  • Non-small cell lung cancer
  • NSCLC
  • Lung cancer
  • RNA-seq
  • Tumor marker