Identification of a novel gene signature related to prognosis and metastasis in gastric cancer

鉴定与胃癌预后和转移相关的新基因特征

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作者:Joseba Elizazu, Aizpea Artetxe-Zurutuza, Maddalen Otaegi-Ugartemendia, Veronica Moncho-Amor, Manuel Moreno-Valladares, Ander Matheu, Estefania Carrasco-Garcia

Background

Gastric Cancer (GC) presents poor outcome, which is consequence of the high incidence of recurrence and metastasis at early stages. GC patients presenting recurrent or metastatic disease display a median life expectancy of only 8 months. The mechanisms underlying GC progression remain poorly understood.

Conclusions

Our study identified a novel signature involved in GC malignancy and prognosis, and revealed a novel pro-metastatic role of ANKRD6 in GC.

Methods

We took advantage of public available GC datasets from TCGA using GEPIA, and identified the matched genes among the 100 genes most significantly associated with overall survival (OS) and disease free survival (DFS).

Results

High expression of ANKRD6, ITIH3, SORCS3, NPY1R and CCDC178 individually and as a signature was associated with poor prognosis and recurrent disease in GC. Moreover, the expression of ANKRD6 and ITIH3 was significantly higher in metastasis and their levels associated to Epithelial to Mesenchymal Transition (EMT) and stemness markers. In line with this, RNAseq analysis revealed genes involved in EMT differentially expressed in ANKRD6 silencing cells. Finally, ANKRD6 silencing in GC metastatic cells showed impairment in GC tumorigenic and metastatic traits in vitro and in vivo. Conclusions: Our study identified a novel signature involved in GC malignancy and prognosis, and revealed a novel pro-metastatic role of ANKRD6 in GC.

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