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

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 TakahashiKazuhiko Nakagawa, Kazuto Nishio

Research output: Contribution to journal › Article › peer-review

18 Citations (Scopus)

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.

Original language	English
Article number	e63249
Journal	PloS one
Volume	8
Issue number	5
DOIs	https://doi.org/10.1371/journal.pone.0063249
Publication status	Published - May 9 2013
Externally published	Yes

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Kurahashi, I., Fujita, Y., Arao, T., Kurata, T., Koh, Y., Sakai, K., Matsumoto, K., Tanioka, M., Takeda, K., Takiguchi, Y., Yamamoto, N., Tsuya, A., Matsubara, N., Mukai, H., Minami, H., Chayahara, N., Yamanaka, Y., Miwa, K., Takahashi, S., ... Nishio, K. (2013). A Microarray-Based Gene Expression Analysis to Identify Diagnostic Biomarkers for Unknown Primary Cancer. PloS one, 8(5), [e63249]. https://doi.org/10.1371/journal.pone.0063249

Kurahashi, I, Fujita, Y, Arao, T, Kurata, T, Koh, Y, Sakai, K, Matsumoto, K, Tanioka, M, Takeda, K, Takiguchi, Y, Yamamoto, N, Tsuya, A, Matsubara, N, Mukai, H, Minami, H, Chayahara, N, Yamanaka, Y, Miwa, K, Takahashi, S, Takahashi, S, Nakagawa, K & Nishio, K 2013, 'A Microarray-Based Gene Expression Analysis to Identify Diagnostic Biomarkers for Unknown Primary Cancer', PloS one, vol. 8, no. 5, e63249. https://doi.org/10.1371/journal.pone.0063249

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title = "A Microarray-Based Gene Expression Analysis to Identify Diagnostic Biomarkers for Unknown Primary Cancer",

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.",

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

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doi = "10.1371/journal.pone.0063249",

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T1 - A Microarray-Based Gene Expression Analysis to Identify Diagnostic Biomarkers for Unknown Primary Cancer

AU - Kurahashi, Issei

AU - Fujita, Yoshihiko

AU - Arao, Tokuzo

AU - Kurata, Takayasu

AU - Koh, Yasuhiro

AU - Sakai, Kazuko

AU - Matsumoto, Koji

AU - Tanioka, Maki

AU - Takeda, Koji

AU - Takiguchi, Yuichi

AU - Yamamoto, Nobuyuki

AU - Tsuya, Asuka

AU - Matsubara, Nobuaki

AU - Mukai, Hirofumi

AU - Minami, Hironobu

AU - Chayahara, Naoko

AU - Yamanaka, Yasuhiro

AU - Miwa, Keisuke

AU - Takahashi, Shin

AU - Takahashi, Shunji

AU - Nakagawa, Kazuhiko

AU - Nishio, Kazuto

PY - 2013/5/9

Y1 - 2013/5/9

N2 - 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.

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

Abstract

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