TGFβ1 overexpression is associated with improved survival and low tumor cell proliferation in patients with early-stage pancreatic ductal adenocarcinoma

Evan Glazer, Eric Welsh, Jose M. Pimiento, Jamie K. Teer, Mokenge P. Malafa

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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 earlystage 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.

Original languageEnglish (US)
Pages (from-to)999-1006
Number of pages8
JournalOncotarget
Volume8
Issue number1
DOIs
StatePublished - Jan 1 2017

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Transforming Growth Factor beta
Adenocarcinoma
Cell Proliferation
Survival
Neoplasms
Pancreaticoduodenectomy
Messenger RNA
Adjuvant Radiotherapy
Atlases
Adjuvant Chemotherapy
Genes
Multivariate Analysis
Genome

All Science Journal Classification (ASJC) codes

  • Oncology

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TGFβ1 overexpression is associated with improved survival and low tumor cell proliferation in patients with early-stage pancreatic ductal adenocarcinoma. / Glazer, Evan; Welsh, Eric; Pimiento, Jose M.; Teer, Jamie K.; Malafa, Mokenge P.

In: Oncotarget, Vol. 8, No. 1, 01.01.2017, p. 999-1006.

Research output: Contribution to journalArticle

Glazer, Evan ; Welsh, Eric ; Pimiento, Jose M. ; Teer, Jamie K. ; Malafa, Mokenge P. / TGFβ1 overexpression is associated with improved survival and low tumor cell proliferation in patients with early-stage pancreatic ductal adenocarcinoma. In: Oncotarget. 2017 ; Vol. 8, No. 1. pp. 999-1006.
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