The anti-apoptotic and prognostic value of fibroblast growth factor 9 in gastric cancer

Abstract

Fibroblast growth factor (FGF) 9 is a member of the FGF family, which promotes carcinogenesis in some solid tumours. However, its biological and prognostic significance in gastric cancer (GC) is unclear. We examined FGF9 expression in 180 GC and corresponding non-tumorous gastric tissue samples by immunohistochemistry and evaluated its role in predicting tumour prognosis. Knockdown of FGF9 by siRNA inhibited cell growth and induced apoptosis in GC cell lines. Fifty of the 180 GC specimens (27.8%) had high FGF9 protein expression, whereas decreased or unchanged expression was observed in 130 cases (72.2%). High FGF9 expression was a significant predictor of poor survival (28.1 vs. 55.8 months, P < 0.001). After stratification according to AJCC stage, FGF9 remained a significant predictor of shorter survival in stage II (30.6 vs. 64.9 months, P < 0.001) and stage III GC (29.7 vs. 58.9 months, P < 0.001). Multivariate and univariate analysis showed that higher expression of FGF9 can be used as a predictor for poor prognosis (HR, 2.95; 95% CI, 1.97–4.41; P < 0.001; and HR, 2.94; 95% CI, 2.01–4.31; P < 0.001, respectively). FGF9 may provide the anti-apoptotic function and be useful as a novel independent marker for evaluating GC prognosis

Molecular alterations in colorectal adenomas and intramucosal adenocarcinomas defined by high-density single-nucleotide polymorphism arrays

“…If the regions at specific loci that we examined contribute to tumour progression, the product of the candidate gene is expected to be overexpressed in a given tissue. Although we could not find minimal common regions of CNAs (more than 30% of cases) in colorectal adenomas and intramucosal adenocarcinomas in the present study, we propose that three candidate genes— FGF9 (which encodes fibroblast growth factor 9), FLT1 (which encodes vascular endothelial growth factor receptor 1, also known as Fms-like tyrosine kinase 1) and KLF5 (which encodes Krüppel-like factor 5), located at 13q11-12, 13q12 and 13q22.1 respectively—may be involved in tumour progression, in agreement with previously published studies ( FGF9 [ 26 , 27 ], FLT1 [ 28 , 29 ] and KLF5 [ 28 – 32 ]). Although these genes are found to be overexpressed in several malignant tumours, including gastric and colon cancers, it remains unclear whether the products of FGF9 , FLT1 and KLF5 are overexpressed in colorectal intramucosal adenocarcinoma [ 26 – 28 , 31 ].…”

CXCR4/CXCR7/CXCL12 axis promotes an invasive phenotype in medullary thyroid carcinoma

“…In breast carcinoma BST2 has been identified as an independent marker for metastasis, its overexpression causing anchorage independent growth and facilitating invasiveness ( Woodman et al , 2016 ). FGF9 on the other hand has been associated with EMT via the upregulation of vascular endothelial growth factor ( Teishima et al , 2014 ) and its expression is linked to poor prognosis and a metastatic phenotype in different solid tumours ( Ueng et al , 2010 ; Ohgino et al , 2014 ; Ren et al , 2016 ). The increased mRNA expression of these markers may be seen as an indicator of the underlying cellular machinery of the CXCR4/CXCR7/CXCL12-mediated metastatic push, but still requires further investigation to fully appreciate the molecular mechanics.…”

Crosstalk Between Cancer Associated Fibroblasts and Cancer Cells in Scirrhous Type Gastric Cancer

“…MMP7 not only has the potential to degrade the extracellular matrix, but also promotes apoptosis evasion in cancer cells. In a Chinese GC cohort study, FGF9 was also associated with accelerated proliferation and apoptosis inhibition of GC cells in an autocrine manner (46).…”