A Microarray-Based Gene Expression Analysis to Identify Diagnostic Biomarkers for Unknown Primary Cancer

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Abstract

Background

The biological basis for cancer of unknown primary (CUP) at the molecular level remains largely unknown, with no evidence of whether a common biological entity exists. Here, we assessed the possibility of identifying a common diagnostic biomarker for CUP using a microarray gene expression analysis.

Methods

Tumor mRNA samples from 60 patients with CUP were analyzed using the Affymetrix U133A Plus 2.0 GeneChip and were normalized by asinh (hyperbolic arc sine) transformation to construct a mean gene-expression profile specific to CUP. A gene-expression profile specific to non-CUP group was constructed using publicly available raw microarray datasets. The t-tests were performed to compare the CUP with non-CUP groups and the top 59 CUP specific genes with the highest fold change were selected ( p-value<0.001).

Results

Among the 44 genes that were up-regulated in the CUP group, 6 genes for ribosomal proteins were identified. Two of these genes ( RPS7 and RPL11) are known to be involved in the Mdm2–p53 pathway. We also identified several genes related to metastasis and apoptosis, suggesting a biological attribute of CUP.

Conclusions

The protein products of the up-regulated and down-regulated genes identified in this study may be clinically useful as unique biomarkers for CUP.

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Author and article information

Contributors

Ming Tat Ling: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, USA )

ISSN (Electronic): 1932-6203

Publication date Collection: 2013

Publication date (Electronic): 9 May 2013

Volume: 8

Issue: 5

Electronic Location Identifier: e63249

Affiliations

[1 ]Department of Planning, Information, and Management, University of Tokyo, Tokyo, Japan

[2 ]Department of Genome Biology, Kinki University School of Medicine, Osaka-Sayama, Japan

[3 ]Department of Medical Oncology, Kinki University School of Medicine, Osaka-Sayama, Japan

[4 ]Division of Drug Discovery and Development, Shizuoka Cancer Center Research Institute, Shizuoka, Japan

[5 ]Medical Oncology Division, Hyogo Cancer Center, Akashi, Japan

[6 ]Department of Clinical Oncology, Osaka City General Hospital, Osaka, Japan

[7 ]Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan

[8 ]Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan

[9 ]Division of Oncology and Hematology, National Cancer Center Hospital East, Chiba, Japan

[10 ]Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe, Japan

[11 ]Department of Medical Oncology, Tochigi Cancer Center, Utsunomiya, Japan

[12 ]Department of Medical Oncology, International Medical Center-Comprehensive Cancer Center, Saitama Medical University, Saitama, Japan

[13 ]Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan

[14 ]Division of Medical Oncology, Cancer Institute Hospital, Tokyo, Japan

Queensland University of Technology, Australia

Author notes

* E-mail: knishio@ 123456med.kindai.ac.jp

Competing Interests: The authors have declared that no competing interests exist.

Conceived and designed the experiments: IK TK YK K. Nakagawa K. Nishio. Performed the experiments: YF YK KS. Analyzed the data: IK YF TA. Contributed reagents/materials/analysis tools: TK K. Matsumoto MT KT YT NY AT NM H. Mukai H. Minami NC YY K. Miwa Shin Takahashi Shunji Takahashi. Wrote the paper: IK YF K. Nishio.

Article

Publisher ID: PONE-D-12-37441

DOI: 10.1371/journal.pone.0063249

PMC ID: 3650062

PubMed ID: 23671674

SO-VID: c5c549b4-5f74-4475-b3f9-ec96427f0869

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 27 November 2012

Date accepted : 1 April 2013

Page count

Pages: 10

Funding

This work was supported by the grant-in-aid for Scientific Research from the Ministry of Health, Labour and Welfare. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

A Microarray-Based Gene Expression Analysis to Identify Diagnostic Biomarkers for Unknown Primary Cancer

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