title: The expression and clinical significance of pSTAT3, VEGF and VEGF-C in pancreatic adenocarcinoma.
abstract: Signal transducers and activators of transcription 3 (STAT3) is a central cytoplasmic transcription factor and regulates a number of pathways important in tumorigenesis including cell cycle progression, apoptosis, tumor angiogenesis, invasion and metastasis.This study aims to investigate the expression of pSTAT3, VEGF and VEGF-C in pancreatic adenocarcinoma and their relations to the clinicopathological features, tumor angiogenesis and prognosis. In the present study, the expression of pSTAT3, VEGF and VEGF-C and microvascular density (MVD) were examined via immunohistochemistry. The clinicopathological information was collected and patients were regularly followed up. The relationship between the parameters and the clinicopathological features were analyzed, and the univariate and multivariate prognostic factors were also analyzed. The expression of pSTAT3 in tumor tissues was significantly higher in contrast to that in normal tissues, and pSTAT3 was related to VEGF and VEGF-C expression, MVD, tumor size, lymphogenous status and TNM staging (P<0.05). Survival analysis suggested that tumor size, TNM staging, pSTAT3 and VEGF expression were risk factors of prognosis, but no independent factors were found. We concluded that pSTAT3, which was a risk factor of prognosis, was abnormally expressed in pancreatic adenocarcinoma and related to tumor size, TNM staging and lymphatic metastasis. pSTAT3 may promote tumor angiogenesis via up-regulating VEGF on protein and even gene levels, and enhance the early lymphatic metastasis through VEGF-C. Better understanding of STAT3 signaling pathways in angiogenesis may contribute to the development of novel therapeutic strategies in angiogenesis and metastasis of pancreatic cancer.
authors.affiliation: Department of General Surgery, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: C
authors.initials: C
authors.lastname: Huang
authors.forename: R
authors.initials: R
authors.lastname: Huang
authors.forename: W
authors.initials: W
authors.lastname: Chang
authors.forename: T
authors.initials: T
authors.lastname: Jiang
authors.forename: K
authors.initials: K
authors.lastname: Huang
authors.forename: J
authors.initials: J
authors.lastname: Cao
authors.forename: X
authors.initials: X
authors.lastname: Sun
authors.forename: Z
authors.initials: Z
authors.lastname: Qiu
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D055806:Microvessels / Q000473:pathology; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D016016:Proportional Hazards Models; D011499:Protein Processing, Post-Translational; D050796:STAT3 Transcription Factor / Q000502:physiology*; D015398:Signal Transduction; D047368:Tumor Burden; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
chemical_list: D009363:Neoplasm Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C467484:VEGFA protein, human; C467486:VEGFC protein, human; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C