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.
Highlights
The precise role of transforming growth factor beta type 1 (TGFβ1) in the progression of pancreatic ductal adenocarcinoma (PDAC) is unknown, and its relation to survival is context dependent [1, 2]
The TGFβ1 signaling pathway activates transcription factors intimately involved in many normal and benign functions that, when commandeered by PDAC, permit the cancer to be refractory to standard therapy
Www.impactjournals.com/oncotarget signaling pathway in 24 pancreatic carcinoma tumors, with 100% of tumors containing at least 1 mutation [25]. While this suggests that the TGFβ1 signaling pathway may be extremely important in PDAC carcinogenesis, it demonstrates that the TGFβ1 signaling pathway may be far more complex than other common mutated pathways
Summary
The precise role of transforming growth factor beta type 1 (TGFβ1) in the progression of pancreatic ductal adenocarcinoma (PDAC) is unknown, and its relation to survival is context dependent [1, 2]. There are conflicting data in the literature regarding the role of TGFβ in patients with early-stage PDAC. Due to these www.impactjournals.com/oncotarget conflicting data, we investigated the association between TGFB1 and RNA expression of the proliferation marker Ki-67 in PDAC.
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