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

Abstract

ObjectivesThe objective of this study was to investigate the role of genetic status of DPC4 in recurrence patterns of resected pancreatic ductal adenocarcinoma (PDAC).MethodsBetween 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.ResultsAnalysis 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.ConclusionsGenetic 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.

Establishment and characterization of 6 novel patient-derived primary pancreatic ductal adenocarcinoma cell lines from Korean pancreatic cancer patients

“…Loss of DPC4 expression is associated with distant metastasis, epithelial to mesenchymal transition, and treatment failure to local recurrence [51–53]. In the present study, all 6 AMCPAC cell lines showed homogeneously intact DPC4 expression.…”

Meta-analysis of recurrence pattern after resection for pancreatic cancer

“…After removal of 690 duplicates, a further 2588 articles were excluded after title and abstract screening because they did not meet the prespecified inclusion criteria. The full texts of the remaining 468 studies were evaluated in more detail, and 89 studies were found to meet the eligibility criteria for this systematic review. Among them, 22 studies containing information on clinical factors relevant to recurrence sites were selected for the meta‐analysis.…”

“…The Cochrane Collaboration tool for assessing risk of bias showed that one study had no domain with a high risk of bias and three studies had one of seven domains with a high risk of bias ( Table S3 , supporting information). The overall risk of bias in non‐randomized studies, according to ROBINS‐I, was moderate in 48 studies and serious in 37 studies ( Table S4 , supporting information).…”

Chemoradiotherapy versus chemotherapy for locally advanced unresectable pancreatic cancer: A systematic review and meta‐analysis

“…For example, biomarkers such as Dpc4/Smad4 and Runx3 have been studied to predict the behavior of the tumor. The expression of Dpc4/Smad4 was investigated in a prospective study and correlated with recurrence pattern and treatment outcome of post‐pancreatectomy patients . Patients with gene loss of Dpc4/Smad4 were more likely to have metastatic recurrence and those with gene expression were more likely to recur locoregionally.…”