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Affymetrix SNP array data for esophageal squamous cell carcinoma samples

ABSTRACT: A proportion of superficial esophageal squamous cell carcinoma, a type of less invasive esophageal squamous cell carcinoma (ESCC), would have metastasis after esophagectomy or endoscopic resection with poor prognosis. The purpose of this study was to discover the whole-genome copy number alteration (CNA) profiles of superficial ESCC and compare the CNAs of superficial ESCC patients with and without metastasis after surgery. Thirty eight superficial ESCC cases, including 19 cases with metastasis and 19 cases without metastasis within 5 years after surgery, were analyzed CNAs by Affymetrix OncoScan™ FFPE Assay. A 39-gene signature was initially constructed to identify high risk of metastasis in superficial ESCC patients. In addition, amplification of 11q13.3 (FGF4) and deletion of 9p21.3 (CDKN2A) were identified as recurrent CNAs across all 38 superficial ESCC cases. And amplifications of 3p26.33 (SOX2-OT), 8q24.21 (MYC), 14q21.1 (FOXA1) and deletion of 3p12.1 (GBE1) were identified as recurrent CNAs among metastasis cases only. Our study provided a 39-gene signature tool to identified high risk metastasis in superficial ESCC and suggested that amplifications of SOX2-OT, MYC, FOXA1 genes and deletion of GBE1 gene might play a vital role in metastasis among superficial ESCC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE78926 | GEO | 2017/06/10

SECONDARY ACCESSION(S): PRJNA314447

REPOSITORIES: GEO

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Project description:Esophageal cancer is one of the most common cancers where TP53 is mutated frequently. Esophageal squamous cell carcinoma (ESCC) is the major subtype of esophageal cancer, and is one of the most lethal cancers worldwide. ESCC evolves often to lung metastasis, which is associated with a dismal prognosis. P53R175H (homologous to Trp53R172H in mice) is a common hot spot mutation. How metastasis is regulated by p53R175H in ESCC, or cancers in general, remains to be elucidated. To investigate p53R175H mediated molecular mechanisms, we utilized germline Trp53R172H/- mice, and generated esophageal specific Trp53-/- mice and Trp53+/+ mice treated with the 4-NQO esophageal-specific carcinogen (a common exposure in humans) to model ESCC. In the primary Trp53R172H/- tumor cell lines established from these mouse models, we depleted Trp53R172H (shTrp53) and observed a marked reduction in cell invasion in vitro and lung metastasis burden in a tail-vein injection model in comparing isogenic cells (shCtrl). Furthermore, to understand the molecular basis for mutant p53 driven lung metastasis, we performed bulk RNA-seq to compare gene expression profiles of metastatic and primary shCtrl and shTrp53 cells. We performed Gene Set Enrichment Analysis (GSEA) and identified the YAP-BIRC5 axis as a potential mediator of Trp53R172H mediated metastasis. As a target gene of YAP, BIRC5 encodes an anti-apoptotic protein, namely survivin. We demonstrate that survivin expression increases in the presence of Trp53R172H but not wild-type Trp53. Furthermore, depletion of survivin decreases Trp53R172H driven lung metastasis. Mechanistically, Trp53R172H but not wild-type Trp53, binds with YAP in ESCC cells, suggesting their cooperation to induce survivin expression. Furthermore, survivin high expression level is associated with increased metastasis in several GI cancer, suggesting that survivin may be a key regulator to metastasis. Taken together, this study unravels new insights into how mutant p53 mediates metastasis.

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Affymetrix SNP array data for esophageal squamous cell carcinoma samples

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