An integrative analysis to identify driver genes in esophageal squamous cell carcinoma

Genta Sawada, Atsushi Niida, Hidenari Hirata, Hisateru Komatsu, Ryutaro Uchi, Teppei Shimamura, Yusuke Takahashi, Junji Kurashige, Tae Matsumura, Hiroki Ueo, Yuki Takano, Masami Ueda, Shotaro Sakimura, Yoshiaki Shinden, Hidetoshi Eguchi, Tomoya Sudo, Keishi Sugimachi, Makoto Yamasaki, Fumiaki Tanaka, Yuji TachimoriYoshiaki Kajiyama, Shoji Natsugoe, Hiromasa Fujita, Yoichi Tanaka, George Calin, Satoru Miyano, Yuichiro Doki, Masaki Mori, Koshi Mimori

研究成果: ジャーナルへの寄稿記事

9 引用 (Scopus)

抄録

Background: Few driver genes have been well established in esophageal squamous cell carcinoma (ESCC). Identification of the genomic aberrations that contribute to changes in gene expression profiles can be used to predict driver genes. Methods: We searched for driver genes in ESCC by integrative analysis of gene expression microarray profiles and copy number data. To narrow down candidate genes, we performed survival analysis on expression data and tested the genetic vulnerability of each genes using public RNAi screening data. We confirmed the results by performing RNAi experiments and evaluating the clinical relevance of candidate genes in an independent ESCC cohort. Results: We found 10 significantly recurrent copy number alterations accompanying gene expression changes, including loci 11q13.2, 7p11.2, 3q26.33, and 17q12, which harbored CCND1, EGFR, SOX2, and ERBB2, respectively. Analysis of survival data and RNAi screening data suggested that GRB7, located on 17q12, was a driver gene in ESCC. In ESCC cell lines harboring 17q12 amplification, knockdown of GRB7 reduced the proliferation, migration, and invasion capacities of cells. Moreover, siRNA targeting GRB7 had a synergistic inhibitory effect when combined with trastuzumab, an anti-ERBB2 antibody. Survival analysis of the independent cohort also showed that high GRB7 expression was associated with poor prognosis in ESCC. Conclusion: Our integrative analysis provided important insights into ESCC pathogenesis. We identified GRB7 as a novel ESCC driver gene and potential new therapeutic target.

元の言語英語
記事番号e0139808
ジャーナルPloS one
10
発行部数10
DOI
出版物ステータス出版済み - 10 14 2015

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squamous cell carcinoma
Genes
genes
Survival Analysis
RNA Interference
Gene expression
Transcriptome
gene expression
Screening
screening
Epithelial Cells
Esophageal Squamous Cell Carcinoma
Microarrays
small interfering RNA
Aberrations
Small Interfering RNA
prognosis
Amplification
Anti-Idiotypic Antibodies
pathogenesis

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

これを引用

Sawada, G., Niida, A., Hirata, H., Komatsu, H., Uchi, R., Shimamura, T., ... Mimori, K. (2015). An integrative analysis to identify driver genes in esophageal squamous cell carcinoma. PloS one, 10(10), [e0139808]. https://doi.org/10.1371/journal.pone.0139808

An integrative analysis to identify driver genes in esophageal squamous cell carcinoma. / Sawada, Genta; Niida, Atsushi; Hirata, Hidenari; Komatsu, Hisateru; Uchi, Ryutaro; Shimamura, Teppei; Takahashi, Yusuke; Kurashige, Junji; Matsumura, Tae; Ueo, Hiroki; Takano, Yuki; Ueda, Masami; Sakimura, Shotaro; Shinden, Yoshiaki; Eguchi, Hidetoshi; Sudo, Tomoya; Sugimachi, Keishi; Yamasaki, Makoto; Tanaka, Fumiaki; Tachimori, Yuji; Kajiyama, Yoshiaki; Natsugoe, Shoji; Fujita, Hiromasa; Tanaka, Yoichi; Calin, George; Miyano, Satoru; Doki, Yuichiro; Mori, Masaki; Mimori, Koshi.

:: PloS one, 巻 10, 番号 10, e0139808, 14.10.2015.

研究成果: ジャーナルへの寄稿記事

Sawada, G, Niida, A, Hirata, H, Komatsu, H, Uchi, R, Shimamura, T, Takahashi, Y, Kurashige, J, Matsumura, T, Ueo, H, Takano, Y, Ueda, M, Sakimura, S, Shinden, Y, Eguchi, H, Sudo, T, Sugimachi, K, Yamasaki, M, Tanaka, F, Tachimori, Y, Kajiyama, Y, Natsugoe, S, Fujita, H, Tanaka, Y, Calin, G, Miyano, S, Doki, Y, Mori, M & Mimori, K 2015, 'An integrative analysis to identify driver genes in esophageal squamous cell carcinoma', PloS one, 巻. 10, 番号 10, e0139808. https://doi.org/10.1371/journal.pone.0139808
Sawada G, Niida A, Hirata H, Komatsu H, Uchi R, Shimamura T その他. An integrative analysis to identify driver genes in esophageal squamous cell carcinoma. PloS one. 2015 10 14;10(10). e0139808. https://doi.org/10.1371/journal.pone.0139808
Sawada, Genta ; Niida, Atsushi ; Hirata, Hidenari ; Komatsu, Hisateru ; Uchi, Ryutaro ; Shimamura, Teppei ; Takahashi, Yusuke ; Kurashige, Junji ; Matsumura, Tae ; Ueo, Hiroki ; Takano, Yuki ; Ueda, Masami ; Sakimura, Shotaro ; Shinden, Yoshiaki ; Eguchi, Hidetoshi ; Sudo, Tomoya ; Sugimachi, Keishi ; Yamasaki, Makoto ; Tanaka, Fumiaki ; Tachimori, Yuji ; Kajiyama, Yoshiaki ; Natsugoe, Shoji ; Fujita, Hiromasa ; Tanaka, Yoichi ; Calin, George ; Miyano, Satoru ; Doki, Yuichiro ; Mori, Masaki ; Mimori, Koshi. / An integrative analysis to identify driver genes in esophageal squamous cell carcinoma. :: PloS one. 2015 ; 巻 10, 番号 10.
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abstract = "Background: Few driver genes have been well established in esophageal squamous cell carcinoma (ESCC). Identification of the genomic aberrations that contribute to changes in gene expression profiles can be used to predict driver genes. Methods: We searched for driver genes in ESCC by integrative analysis of gene expression microarray profiles and copy number data. To narrow down candidate genes, we performed survival analysis on expression data and tested the genetic vulnerability of each genes using public RNAi screening data. We confirmed the results by performing RNAi experiments and evaluating the clinical relevance of candidate genes in an independent ESCC cohort. Results: We found 10 significantly recurrent copy number alterations accompanying gene expression changes, including loci 11q13.2, 7p11.2, 3q26.33, and 17q12, which harbored CCND1, EGFR, SOX2, and ERBB2, respectively. Analysis of survival data and RNAi screening data suggested that GRB7, located on 17q12, was a driver gene in ESCC. In ESCC cell lines harboring 17q12 amplification, knockdown of GRB7 reduced the proliferation, migration, and invasion capacities of cells. Moreover, siRNA targeting GRB7 had a synergistic inhibitory effect when combined with trastuzumab, an anti-ERBB2 antibody. Survival analysis of the independent cohort also showed that high GRB7 expression was associated with poor prognosis in ESCC. Conclusion: Our integrative analysis provided important insights into ESCC pathogenesis. We identified GRB7 as a novel ESCC driver gene and potential new therapeutic target.",
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T1 - An integrative analysis to identify driver genes in esophageal squamous cell carcinoma

AU - Sawada, Genta

AU - Niida, Atsushi

AU - Hirata, Hidenari

AU - Komatsu, Hisateru

AU - Uchi, Ryutaro

AU - Shimamura, Teppei

AU - Takahashi, Yusuke

AU - Kurashige, Junji

AU - Matsumura, Tae

AU - Ueo, Hiroki

AU - Takano, Yuki

AU - Ueda, Masami

AU - Sakimura, Shotaro

AU - Shinden, Yoshiaki

AU - Eguchi, Hidetoshi

AU - Sudo, Tomoya

AU - Sugimachi, Keishi

AU - Yamasaki, Makoto

AU - Tanaka, Fumiaki

AU - Tachimori, Yuji

AU - Kajiyama, Yoshiaki

AU - Natsugoe, Shoji

AU - Fujita, Hiromasa

AU - Tanaka, Yoichi

AU - Calin, George

AU - Miyano, Satoru

AU - Doki, Yuichiro

AU - Mori, Masaki

AU - Mimori, Koshi

PY - 2015/10/14

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N2 - Background: Few driver genes have been well established in esophageal squamous cell carcinoma (ESCC). Identification of the genomic aberrations that contribute to changes in gene expression profiles can be used to predict driver genes. Methods: We searched for driver genes in ESCC by integrative analysis of gene expression microarray profiles and copy number data. To narrow down candidate genes, we performed survival analysis on expression data and tested the genetic vulnerability of each genes using public RNAi screening data. We confirmed the results by performing RNAi experiments and evaluating the clinical relevance of candidate genes in an independent ESCC cohort. Results: We found 10 significantly recurrent copy number alterations accompanying gene expression changes, including loci 11q13.2, 7p11.2, 3q26.33, and 17q12, which harbored CCND1, EGFR, SOX2, and ERBB2, respectively. Analysis of survival data and RNAi screening data suggested that GRB7, located on 17q12, was a driver gene in ESCC. In ESCC cell lines harboring 17q12 amplification, knockdown of GRB7 reduced the proliferation, migration, and invasion capacities of cells. Moreover, siRNA targeting GRB7 had a synergistic inhibitory effect when combined with trastuzumab, an anti-ERBB2 antibody. Survival analysis of the independent cohort also showed that high GRB7 expression was associated with poor prognosis in ESCC. Conclusion: Our integrative analysis provided important insights into ESCC pathogenesis. We identified GRB7 as a novel ESCC driver gene and potential new therapeutic target.

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