A microarray-based gene expression analysis to identify diagnostic biomarkers for unknown primary cancer

Issei Kurahashi; Yoshihiko Fujita; Tokuzo Arao; Takayasu Kurata; Yasuhiro Koh; Kazuko Sakai; Koji Matsumoto; Maki Tanioka; Koji Takeda; Yuichi Takiguchi; Nobuyuki Yamamoto; Asuka Tsuya; Nobuaki Matsubara; Hirofumi Mukai; Hironobu Minami; Naoko Chayahara; Yasuhiro Yamanaka; Keisuke Miwa; Shin Takahashi; Shunji Takahashi; Kazuhiko Nakagawa; Kazuto Nishio

doi:10.1371/journal.pone.0063249

A microarray-based gene expression analysis to identify diagnostic biomarkers for unknown primary cancer

PLoS One. 2013 May 9;8(5):e63249. doi: 10.1371/journal.pone.0063249. Print 2013.

Affiliation

¹ Department of Planning, Information, and Management, University of Tokyo, Tokyo, Japan.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers, Tumor / classification
Biomarkers, Tumor / genetics*
Biomarkers, Tumor / metabolism
Cluster Analysis
Gene Expression Profiling*
Gene Expression Regulation, Neoplastic*
Humans
Neoplasms, Unknown Primary / diagnosis
Neoplasms, Unknown Primary / genetics*
Neoplasms, Unknown Primary / metabolism
Oligonucleotide Array Sequence Analysis / methods*
Up-Regulation

Substances

Biomarkers, Tumor

Associated data

GEO/GSE42392

Grants and 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.