PLoS ONE (Jan 2013)

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
https://doi.org/10.1371/journal.pone.0063249
Journal volume & issue
Vol. 8, no. 5
p. e63249

Abstract

Read online

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.