RGD Reference Report - An Integrative Analysis to Identify Driver Genes in Esophageal Squamous Cell Carcinoma. - Rat Genome Database

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An Integrative Analysis to Identify Driver Genes in Esophageal Squamous Cell Carcinoma.

Authors: 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 
Citation: Sawada G, etal., PLoS One. 2015 Oct 14;10(10):e0139808. doi: 10.1371/journal.pone.0139808. eCollection 2015.
RGD ID: 151347661
Pubmed: PMID:26465158   (View Abstract at PubMed)
PMCID: PMC4605796   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0139808   (Journal Full-text)


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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GRB7Humanesophagus squamous cell carcinoma exacerbatesHEP mRNA:increased expression:esophagus mucosa (human)RGD 

Objects Annotated

Genes (Homo sapiens)
GRB7  (growth factor receptor bound protein 7)


Additional Information