Circular RNA Fibroblast Growth Factor Receptor 1 Promotes Pancreatic Cancer Progression by Targeting MicroRNA-532-3p/PIK3CB Axis.

OBJECTIVE: The aim of the study is to explore the contribution and mechanism of circular RNA fibroblast growth factor receptor 1 (circFGFR1) in pancreatic ductal adenocarcinoma (PDAC) progression. METHODS: Expressions of circFGFR1, microRNA (miR)-532-3p, and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta (PIK3CB) were assessed by quantitative real-time polymerase chain reaction or in situ hybridization. Fluorescence in situ hybridization determined the subcellular localization of circFGFR1. Immunohistochemistry was used to detect PIK3CB expression in PDAC tissues. Cell growth was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assays. Wound healing, transwell, and flow cytometry assays examined the migration, invasion, and apoptosis. Dual-luciferase and RNA pull-down assay verified the interactions between circFGFR1/PIK3CB and miR-532-3p. In vivo xenograft tumor growth and lung metastasis were assessed in nude mice. RESULTS: Functionally, knockdown of circFGFR1 restrained in vitro PDAC cell growth, migration, invasion, and in vivo xenograft tumor growth and lung metastasis. In addition, circFGFR1 could sponge miR-532-3p to upregulate PIK3CB level. Rescue experiments revealed that the tumor-suppressive effects caused by miR-532-3p mimics could be reversed by circFGFR1 or PIK3CB overexpression. CONCLUSIONS: Our data revealed that circFGFR1 driven the malignant progression of PDAC by targeting miR-532-3p/PIK3CB axis, suggesting that inhibition of circFGFR1 might be considered as a therapeutic target for PDAC.

Carcinoma of the ampulla of Vater: factors influencing long-term survival of 127 patients with resection.

INTRODUCTION: The prognosis for patients with carcinoma of the ampulla of Vater is improved relative to other periampullary neoplasms. Identification of independent prognostic factors in ampullary carcinomas has been limited by the small number of tumors resected. The aim of the present study was to determine the clinicopathologic factors that influence long-term survival in patients with resected ampullary carcinoma. METHODS: Clinicopathologic data were retrospectively reviewed for patients with ampullary carcinomas radically resected between March 1987 and September 2002. The correlation between clinicopathologic variables and survival of patients after resection was examined by the Kaplan-Meier method, the log-rank test, and Cox proportional hazards regression. Ampullary carcinomas were radically resected in 127 patients either by pancreaticoduodenectomy (n = 124) or local resection (n = 3). RESULTS: Hospital mortality was 9.7%. The overall actuarial survival rates (including hospital deaths) at 1, 3, 5, and 10 years were 76.2%, 46.8%, 43.3%, and 35.7%, respectively. Factors that significantly influenced survival were lymph node status (P < 0.001), depth of tumor infiltration (P = 0.029), and TNM stage (P < 0.001) on univariate analysis. On multivariate analysis, both depth of infiltration and lymph node status were the independent determinants of survival after resection (P = 0.003, P = 0.005, respectively). CONCLUSIONS: Carcinoma of the ampulla of Vater has a higher resectability rate and a much better survival rate than pancreatic cancer. Pancreaticoduodenectomy is the treatment of choice for this tumor. Long-term survival was independently influenced by the depth of tumor infiltration and lymph node metastasis.