Gene expression signature and the prediction of ulcerative colitis-associated colorectal cancer by DNA microarray

Toshiaki Watanabe, Takashi Kobunai, Etsuko Toda, Takamitsu Kanazawa, Yoshihiro Kazama, Junichiro Tanaka, Toshiaki Tanaka, Yoko Yamamoto, Keisuke Hata, Tetsu Kojima, Tadashi Yokoyama, Tsuyoshi Konishi, Yoshihiro Okayama, Yoshikazu Sugimoto, Toshinori Oka, Shin Sasaki, Yohichi Ajioka, Tetsuichiro Muto, Hirokazu Nagawa

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Purpose: Ulcerative colitis (UC) is associated with a high risk of colorectal cancer. To identify genes that could predict the development of cancer in UC, we conducted a DNA microarray analysis using nonneoplastic rectal mucosa of UC patients. Experimental Design: Gene expression in nonneoplastic mucosa of 53 UC patients were examined. Gene expression profiles were examined using human Genome U133 Plus 2.0 gene chip array (Affymetrix). Among 53 UC patients, 10 had UC-associated cancer (UC-Ca group) whereas 43 did not (UC-NonCa group). Results: By comparing gene expression profiles of nonneoplastic rectal mucosae between the UC-Ca and UC-NonCa groups, we could identify 40 genes that were differentially expressed between two groups. The list of discriminating genes included low-density lipoprotein receptor-related protein (LRP5 and LRP6). Previous studies suggested that LRP5 and LRP6 expression promotes cancer cell proliferation and tumorigenesis and are considered as candidate oncogenes. In the present study, both LRP5 and LRP6 showed significantly higher expression in the UC-Ca group, which suggests the importance of these genes in the development of UC-associated colorectal cancers. With the 40 selected discriminating genes, we did class prediction of the development of colorectal neoplasms in UC patients. Using the k-nearest neighbor method and the support vector machine, we could predict the development of UC-associated neoplasms with an accuracy of 86.8% and 98.1%, respectively. Conclusions: These findings have important implications for the early detection of malignant lesions in UC and may provide directions for future research into the molecular mechanisms of UC-associated cancer.

Original languageEnglish
Pages (from-to)415-420
Number of pages6
JournalClinical Cancer Research
Volume13
Issue number2 I
DOIs
Publication statusPublished - 2007 Jan 15
Externally publishedYes

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Oligonucleotide Array Sequence Analysis
Ulcerative Colitis
Transcriptome
Colorectal Neoplasms
Mucous Membrane
Genes
Neoplasms
LDL-Receptor Related Proteins
LDL Receptors
Human Genome
Microarray Analysis
Oncogenes
Carcinogenesis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Gene expression signature and the prediction of ulcerative colitis-associated colorectal cancer by DNA microarray. / Watanabe, Toshiaki; Kobunai, Takashi; Toda, Etsuko; Kanazawa, Takamitsu; Kazama, Yoshihiro; Tanaka, Junichiro; Tanaka, Toshiaki; Yamamoto, Yoko; Hata, Keisuke; Kojima, Tetsu; Yokoyama, Tadashi; Konishi, Tsuyoshi; Okayama, Yoshihiro; Sugimoto, Yoshikazu; Oka, Toshinori; Sasaki, Shin; Ajioka, Yohichi; Muto, Tetsuichiro; Nagawa, Hirokazu.

In: Clinical Cancer Research, Vol. 13, No. 2 I, 15.01.2007, p. 415-420.

Research output: Contribution to journalArticle

Watanabe, T, Kobunai, T, Toda, E, Kanazawa, T, Kazama, Y, Tanaka, J, Tanaka, T, Yamamoto, Y, Hata, K, Kojima, T, Yokoyama, T, Konishi, T, Okayama, Y, Sugimoto, Y, Oka, T, Sasaki, S, Ajioka, Y, Muto, T & Nagawa, H 2007, 'Gene expression signature and the prediction of ulcerative colitis-associated colorectal cancer by DNA microarray', Clinical Cancer Research, vol. 13, no. 2 I, pp. 415-420. https://doi.org/10.1158/1078-0432.CCR-06-0753
Watanabe, Toshiaki ; Kobunai, Takashi ; Toda, Etsuko ; Kanazawa, Takamitsu ; Kazama, Yoshihiro ; Tanaka, Junichiro ; Tanaka, Toshiaki ; Yamamoto, Yoko ; Hata, Keisuke ; Kojima, Tetsu ; Yokoyama, Tadashi ; Konishi, Tsuyoshi ; Okayama, Yoshihiro ; Sugimoto, Yoshikazu ; Oka, Toshinori ; Sasaki, Shin ; Ajioka, Yohichi ; Muto, Tetsuichiro ; Nagawa, Hirokazu. / Gene expression signature and the prediction of ulcerative colitis-associated colorectal cancer by DNA microarray. In: Clinical Cancer Research. 2007 ; Vol. 13, No. 2 I. pp. 415-420.
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abstract = "Purpose: Ulcerative colitis (UC) is associated with a high risk of colorectal cancer. To identify genes that could predict the development of cancer in UC, we conducted a DNA microarray analysis using nonneoplastic rectal mucosa of UC patients. Experimental Design: Gene expression in nonneoplastic mucosa of 53 UC patients were examined. Gene expression profiles were examined using human Genome U133 Plus 2.0 gene chip array (Affymetrix). Among 53 UC patients, 10 had UC-associated cancer (UC-Ca group) whereas 43 did not (UC-NonCa group). Results: By comparing gene expression profiles of nonneoplastic rectal mucosae between the UC-Ca and UC-NonCa groups, we could identify 40 genes that were differentially expressed between two groups. The list of discriminating genes included low-density lipoprotein receptor-related protein (LRP5 and LRP6). Previous studies suggested that LRP5 and LRP6 expression promotes cancer cell proliferation and tumorigenesis and are considered as candidate oncogenes. In the present study, both LRP5 and LRP6 showed significantly higher expression in the UC-Ca group, which suggests the importance of these genes in the development of UC-associated colorectal cancers. With the 40 selected discriminating genes, we did class prediction of the development of colorectal neoplasms in UC patients. Using the k-nearest neighbor method and the support vector machine, we could predict the development of UC-associated neoplasms with an accuracy of 86.8{\%} and 98.1{\%}, respectively. Conclusions: These findings have important implications for the early detection of malignant lesions in UC and may provide directions for future research into the molecular mechanisms of UC-associated cancer.",
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T1 - Gene expression signature and the prediction of ulcerative colitis-associated colorectal cancer by DNA microarray

AU - Watanabe, Toshiaki

AU - Kobunai, Takashi

AU - Toda, Etsuko

AU - Kanazawa, Takamitsu

AU - Kazama, Yoshihiro

AU - Tanaka, Junichiro

AU - Tanaka, Toshiaki

AU - Yamamoto, Yoko

AU - Hata, Keisuke

AU - Kojima, Tetsu

AU - Yokoyama, Tadashi

AU - Konishi, Tsuyoshi

AU - Okayama, Yoshihiro

AU - Sugimoto, Yoshikazu

AU - Oka, Toshinori

AU - Sasaki, Shin

AU - Ajioka, Yohichi

AU - Muto, Tetsuichiro

AU - Nagawa, Hirokazu

PY - 2007/1/15

Y1 - 2007/1/15

N2 - Purpose: Ulcerative colitis (UC) is associated with a high risk of colorectal cancer. To identify genes that could predict the development of cancer in UC, we conducted a DNA microarray analysis using nonneoplastic rectal mucosa of UC patients. Experimental Design: Gene expression in nonneoplastic mucosa of 53 UC patients were examined. Gene expression profiles were examined using human Genome U133 Plus 2.0 gene chip array (Affymetrix). Among 53 UC patients, 10 had UC-associated cancer (UC-Ca group) whereas 43 did not (UC-NonCa group). Results: By comparing gene expression profiles of nonneoplastic rectal mucosae between the UC-Ca and UC-NonCa groups, we could identify 40 genes that were differentially expressed between two groups. The list of discriminating genes included low-density lipoprotein receptor-related protein (LRP5 and LRP6). Previous studies suggested that LRP5 and LRP6 expression promotes cancer cell proliferation and tumorigenesis and are considered as candidate oncogenes. In the present study, both LRP5 and LRP6 showed significantly higher expression in the UC-Ca group, which suggests the importance of these genes in the development of UC-associated colorectal cancers. With the 40 selected discriminating genes, we did class prediction of the development of colorectal neoplasms in UC patients. Using the k-nearest neighbor method and the support vector machine, we could predict the development of UC-associated neoplasms with an accuracy of 86.8% and 98.1%, respectively. Conclusions: These findings have important implications for the early detection of malignant lesions in UC and may provide directions for future research into the molecular mechanisms of UC-associated cancer.

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