title: Sprouty2 correlates with favorable prognosis of gastric adenocarcinoma via suppressing FGFR2-induced ERK phosphorylation and cancer progression.
abstract: Fibroblast growth factor receptor 2 (FGFR2) has been identified as a predictive biomarker for unfavorable prognosis of gastric adenocarcinoma. As a well-defined antagonist in FGFR2-induced RAS/ERK activation, ectopic expression of sprouty (SPRY) family was reported in several kinds of cancers except gastric cancer. To explore the clinical significance of SPRY family and its correlation with FGFR2, we detected the expression of FGFR2 and SPRY family in 104 cases of gastric adenocarcinoma and subsequently analyzed their correlations with clinicopathological factors and overall survival rates by univariate and multivariate analysis. As the result, we demonstrated that both FGFR2 high-expression and SPRY2 low-expression indicated poorer prognosis of gastric adenocarcinoma. SPRY2 low-expression was significantly associated with FGFR2 high-expression, positive lymphatic invasion and metastasis. We further proved that SPRY2 could suppress FGFR2-induced ERK phosphorylation, cell proliferation and invasion with experiments in vitro and in vivo. In conclusion, we demonstrated that SPRY2 low-expression is a biomarker for unfavorable prognosis in gastric adenocarcinoma. SPRY2 can antagonize FGFR2-induced proliferation and invasion via suppressing ERK phosphorylation in gastric cancer cells, indicating SPRY2 as a potential therapeutic target for gastric adenocarcinoma treatment.
authors.affiliation: Department of General Surgery, Qilu Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Pathology, Qianfoshan Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Neurology, Yidu Central Hospital of Weifang City, Weifang, Shandong, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Hospital of People's Liberation Army, Beijing, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of General Surgery, Qilu Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of General Surgery, Qilu Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Sayed
authors.initials: S
authors.lastname: Ismail
authors.affiliation: Department of General Surgery, Qilu Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Hongda
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Yidu Central Hospital of Weifang City, Weifang, Shandong, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of General Surgery, Qilu Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Zongli
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Qilu Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pathology, Qianfoshan Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Sun
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D011379:Prognosis; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016019:Survival Analysis
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C485561:SPRY2 protein, human; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: FGFR2; SPRY2; gastric adenocarcinoma; invasion; proliferation