title: TGFβ1 overexpression is associated with improved survival and low tumor cell proliferation in patients with early-stage pancreatic ductal adenocarcinoma.
abstract: The role of transforming growth factor beta-type-1 (TGFβ1) in pancreatic ductal adenocarcinoma (PDAC) progression is stage-dependent. We hypothesized that TGFβ1 expression is associated with survival and proliferation markers in patients with early-stage PDAC. We acquired clinicopathologic, treatment, and mRNA expression data from The Cancer Genome Atlas data set for 106 patients identified with stage I/II PDAC who underwent pancreaticoduodenectomy. Patients were categorized as high expression when mRNA expression was ≥75th percentile for each gene. Average log2 mRNA expression of TGFβ1 in patients with high expression was 11.6 ± 0.2 and 10.5 ± 0.6 in patients with low expression (P<0.001). Low TGFβ1 expression is associated with shorter median survival compared with high TGFβ1 expression (17 versus at least 60 months; P=0.005). Patients with tumors demonstrating high MKI67 (the gene encoding Ki-67) expression have shorter median survival versus those with lowerMKI67 expression (16 versus 20 months; P=0.026). TGFβ1 and MKI67 are inversely associated (P=0.009). On multivariate analysis, improved survival is associated with TGFβ1 overexpression (P=0.017), adjuvant chemotherapy (P=0.001), and adjuvant radiotherapy (P=0.017), whereas positive surgical margins are associated with worse survival (P=0.002). In patients who undergo pancreaticoduodenectomy for PDAC, high TGFβ1 expression may counteract the worse survival associated with high proliferation.
authors.affiliation: Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.|Department of Surgery, University of Tennessee Health Sciences Center, Memphis, TN, USA.
authors.forename: Evan S
authors.initials: ES
authors.lastname: Glazer
authors.affiliation: Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Welsh
authors.affiliation: Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Pimiento
authors.affiliation: Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: Jamie K
authors.initials: JK
authors.lastname: Teer
authors.affiliation: Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: Mokenge P
authors.initials: MP
authors.lastname: Malafa
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D049109:Cell Proliferation; D016208:Databases, Factual; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1
keywords: Ki-67; MKI67; TGF-β; pancreatic carcinoma