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Cited by 57Pancreatic and Hepatic Oncology ResearchCholangiocarcinoma and Gallbladder Cancer StudiesNeuroendocrine Tumor Research Advances

The DPC4/SMAD4 genetic status determines recurrence patterns and treatment outcomes in resected pancreatic ductal adenocarcinoma: A prospective cohort study

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Shin, Sang Hyun, Kim, Hwa Jung, Hwang, Dae Wook, Lee, Jae Hoon, Song, Ki Byung, Jun, Eunsung, Shim, In Kyong, Hong, Seung-Mo +4 more·2017·Oncotarget
DOI 10.18632/oncotarget.14901PMC PMC5392299
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Abstract

// Sang Hyun Shin 1, * , Hwa Jung Kim 2, * , Dae Wook Hwang 1 , Jae Hoon Lee 1 , Ki Byung Song 1 , Eunsung Jun 3 , In Kyong Shim 4 , Seung-Mo Hong 5 , Hyoung Jung Kim 6 , Kwang-Min Park 1 , Young-Joo Lee 1 , Song Cheol Kim 1 1 Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea 2 Department of Preventive Medicine, University of Ulsan College of Medicine, Seoul, South Korea 3 Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, South Korea 4 Biomedical Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, South Korea 5 Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea 6 Department of Radiology and the Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea * These authors have contributed equally to this work Correspondence to: Song Cheol Kim, email: drksc@amc.seoul.kr Keywords: pancreatic ductal adenocarcinoma, pancreatic cancer, DPC4, SMAD4 Received: October 02, 2016 Accepted: December 31, 2016 Published: January 30, 2017 ABSTRACT Objectives: The objective of this study was to investigate the role of genetic status of DPC4 in recurrence patterns of resected pancreatic ductal adenocarcinoma (PDAC). Methods: Between April 2004 and December 2011, data on patients undergoing surgical resection for PDAC were reviewed. Genetic status of DPC4 was determined and correlated to recurrence patterns and clinical outcomes. Results: Analysis of 641 patients revealed that genetic status of DPC4 was associated with overall survival and was highly correlated with recurrence patterns, as inactivation of the DPC4 gene was the strongest predictor of metastatic recurrence (odds ratio = 4.28). Treatment modalities for recurrent PDAC included chemotherapy alone and concurrent chemotherapy along with local control. For both locoregional and metastatic recurrence, local control resulted in improved survival; however, for groups subdivided according to recurrence patterns and genetic status of DPC4 , local control contributed to improved survival in locoregional recurrences of patients with expressed DPC4 , while chemotherapy alone was sufficient for others. Conclusions: Genetic status of DPC4 contributes to the recurrence patterns following pancreatectomy, and patients with an initially expressed DPC4 gene receive a greater benefit from intensive local control for locoregional recurrence. The DPC4 gene, therefore, may aid the establishment of treatment strategies for initial adjuvant treatment or for recurrent PDAC.

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  • DPC4 gene frequently experiences inactivation in PDAC, leading to enhanced metastasis and worse prognosis.

    “The DPC4 gene, encoding SMAD4, frequently experiences inactivation in PDAC, leading to enhanced metastasis and worse prognosis.”

    From Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer (2024) · cites this paper as [72]

    The Introduction says DPC4 is inactivated in 55–80% of PDACs. The Results report more metastatic recurrence and shorter overall survival in patients with inactivated DPC4, but establish associations rather than showing that inactivation causes metastasis or worse prognosis. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • SMAD4 loss is associated with distant metastases.

    “Notably, SMAD4 loss is associated with distant metastases, highlighting its role in disease progression patterns [72,73,74,75,76,118].”

    From Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer (2024) · cites this paper as [72]

  • Patients with DPC4-expressed cancers exhibit longer survival.

    “Patients with DPC4-expressed cancers exhibit longer survival, emphasizing the significance of SMAD4 in treatment outcomes.”

    From Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer (2024) · cites this paper as [72]

  • Patients with inactivated DPC4 gene function have a higher risk of metastatic recurrence, with DPC4 inactivation being the most strongly correlated factor.

    “Patients with an inactivated DPC4 gene function have a higher risk of metastatic recurrence, with DPC4 inactivation being the most strongly correlated factor.”

    From Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer (2024) · cites this paper as [72]

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Authors
Shin, S. H., Kim, H. J., Hwang, D. W., Lee, J. H., Song, K. B., Jun, E., Shim, I. K., Hong, S.-M., Kim, H. J., Park, K.-M., Lee, Y.-J., & Kim, S. C.
Affiliations
  • Asan Medical Center (KR)
  • University of Ulsan (KR)
Corresponding author
  • Shin, Sang Hyun
  • Kim, Hwa Jung
ORCID
Venue
Oncotarget
Publisher
Impact Journals, LLC
Published
2017-01-30
Volume
8
Issue
11
Pages
17945-17959
ISSN
1949-2553 (ISSN-L)
DOI
10.18632/oncotarget.14901
PMC
PMC5392299
OpenAlex
W2585332013
Cited by
57
References
4
Citations by year
2026: 2 · 2025: 1 · 2024: 5 · 2023: 18 · 2022: 5 · 2021: 5 · 2020: 2 · 2019: 7 · 2018: 5 · 2017: 7
FWCI
2.53
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Oncotarget (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Asan Institute for Life Sciences, Asan Medical Center
Topics
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
  • Health Sciences › Medicine › Surgery › Cholangiocarcinoma and Gallbladder Cancer Studies
  • Health Sciences › Medicine › Epidemiology › Neuroendocrine Tumor Research Advances
Keywords
pancreatic ductal adenocarcinoma, SMAD4, gene inactivation, tumor recurrence patterns, distant recurrence, locoregional recurrence, overall survival, local control, adjuvant chemotherapy, prognostic factors, surgical resection, recurrence-free survival, recurrence-free interval
MeSH terms
Adult, Aged, Aged, 80 and over, Female, Humans, Immunohistochemistry, Male, Middle Aged, Neoplasm Recurrence, Local, Pancreatic Neoplasms, Prognosis, Prospective Studies, Biomarkers, Tumor, Cohort Studies, Carcinoma, Pancreatic Ductal, Smad4 Protein, Kaplan-Meier Estimate, Young Adult

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