SMAD4 Expression Predicts Local Spread and Treatment Failure in Resected Pancreatic Cancer
Abstract
OBJECTIVE: The purpose of this study was to evaluate the prognostic relevance of SMAD4 expression in pancreatic cancer. METHODS: We analyzed the correlations between SMAD4 expression and clinicopathological parameters and outcome in 174 patients with pancreatic cancer. Specimens were also classified into subtypes reflecting epithelial-to-mesenchymal transition, based on E-cadherin and vimentin. RESULTS: We found that 59.8% (104/174) of patients were SMAD4 and 40.2% (70/174) were SMAD4. Disease-specific survival in patients with SMAD4 was significantly better than that in SMAD4. SMAD4 status was significantly correlated with portal vein invasion, lymph vessel invasion, and perineural invasion and was an independent prognostic factor. SMAD4 was significantly associated with mesenchymal phenotype. The loss of SMAD4 expression was found in 49.4% of patients with no vascular invasion, 61.9% with portal vein invasion, 76.5% with common hepatic artery invasion, and 80.8% with superior mesenteric artery invasion. In addition, the specimens from 59.0% of patients with local recurrence, 66.7% of those with both local and distant recurrence, and 73.7% of those with distant recurrence were SMAD4. CONCLUSIONS: The loss of SMAD4 expression is an independent prognostic factor and seems to be associated with tumor progression, pattern of failure, and epithelial-to-mesenchymal transition status. Preoperative stratification based on SMAD4 could lead to appropriate treatment strategy.
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Multivariate analysis identified SMAD4− as the most prominent prognostic factor for PDAC, alongside elevated CA19-9 levels and metastatic characteristics.
“Multivariate analysis identified SMAD4− as the most prominent prognostic factor for PDAC, emphasizing its significance alongside other factors like elevated CA19-9 levels and metastatic characteristics [79].”
From Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer (2024) · cites this paper as [79]
In one study, 59.8% of specimens were SMAD4−, correlating significantly with adverse clinicopathological parameters and adverse EMT status.
“In one study, 59.8% of specimens were SMAD4−, correlating significantly with adverse clinicopathological parameters and adverse EMT status.”
From Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer (2024) · cites this paper as [79]
Patients with SMAD4+ experienced significantly better disease-specific and disease-free survival compared to SMAD4− counterparts.
“Patients with SMAD4+ experienced significantly better disease-specific and disease-free survival compared to their SMAD4− counterparts.”
From Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer (2024) · cites this paper as [79]
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- Authors
- Yamada, S., Fujii, T., Shimoyama, Y., Kanda, M., Nakayama, G., Sugimoto, H., Koike, M., Nomoto, S., Fujiwara, M., Nakao, A., & Kodera, Y.
- Affiliations
- Nagoya University Hospital (JP)
- Nagoya Central Hospital (JP)
- Corresponding author
- Yamada, Suguru
- Fujii, Tsutomu
- Kanda, Mitsuro
- Nakayama, Goro
- Sugimoto, Hiroyuki
- Koike, Masahiko
- Nomoto, Shuji
- Fujiwara, Michitaka
- Kodera, Yasuhiro
- Venue
- Pancreas
- Published
- 2015-05
- Volume
- 44
- Issue
- 4
- Pages
- 660-664
- ISSN
- 0885-3177 (ISSN-L)
- OpenAlex
- W2005272613
- Cited by
- 71
- References
- 27
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 2 · 2022: 6 · 2021: 10 · 2020: 9 · 2019: 6 · 2018: 10 · 2017: 8 · 2016: 8 · 2015: 3
- FWCI
- 4.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pancreas (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Surgery › Cholangiocarcinoma and Gallbladder Cancer Studies
- Keywords
- SMAD4, pancreatic cancer, prognostic factors, SMAD4 loss, epithelial-mesenchymal transition, portal vein invasion, lymph vessel invasion, perineural invasion, local recurrence, disease-specific survival, vimentin, E-cadherin, resected pancreatic cancer
- MeSH terms
- Adult, Aged, Aged, 80 and over, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neoplasm Invasiveness, Neoplasm Recurrence, Local, Pancreatectomy, Pancreatic Neoplasms, Prognosis, Biomarkers, Tumor, Pancreaticoduodenectomy, Treatment Failure, Disease Progression, Carcinoma, Pancreatic Ductal, Smad4 Protein, Epithelial-Mesenchymal Transition
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