Intratumoral Heterogeneity of SMAD4 Immunohistochemical Expression and Its Role in Prediction of Recurrence Pattern in Patients with Resectable Pancreatic Cancer

Pokataev, Ilya; Кудайбергенова, А. Г.; Artemyeva, Anna; Popova, Anna; Rumyantsev, А. А.; Подлужный, Д. В.; Кудашкин, Н. Е.; Fedyanin, Mikhail; Tryakin, А. А.; Tjulandin, S.

doi:10.1007/s12029-018-0103-6

Cited by 4 publications

(3 citation statements)

References 16 publications

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“…undetectable hepatic sinusoidal metastases. SMAD4 mutation, which has been associated with portal vein invasion, metastatic disease, and poor survival in PDAC (23)(24)(25)(26), was not associated with development of ascites in our data; however, it is possible that in these patients splanchnic vessel invasion may be occurring independently of SMAD4, and SMAD4 status has failed to predict locoregional recurrence after excision (27,28).…”

Section: Discussioncontrasting

confidence: 58%

Ascites Is a Poor Prognostic Factor in Advanced Pancreatic Adenocarcinoma and May Be Undertreated: A Prospective Cohort Study

Wang,

Cui,

Osipov

et al. 2024

Clin Transl Gastroenterol

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Pancreatic ductal adenocarcinoma (PDAC) is associated with significant morbidity and mortality as most patients present with advanced disease. The development of ascites has been associated with poor outcomes and further characterization and contemporary management strategies are needed. 437 patients enrolled in the Gastrointestinal Biobank at Cedars-Sinai Medical Center who had epithelial pancreatic malignancy were included in the prospective cohort group. 41.7% of patients included in the study developed ascites. The majority (>80%) of ascites patients had high serum-ascites albumin gradient (SAAG) ascites. In both univariate and multivariate analysis, history of >=1 form of chemotherapy was significantly associated with ascites. Estimated median OS in patients with ascites was significantly lower than in patients without ascites, 473 days vs. 573 days, and ascites had a HR of 1.37. Patients with ascites who received diuretics and indwelling peritoneal catheter had an estimated median survival of 133 days from diagnosis of ascites, and those that received only the indwelling peritoneal catheter without diuretics had an estimated median survival of only 54 days. The estimated median survival from the diagnosis of ascites was 92 days and median time to puncture was 7 days. Median time from first tap to death was 45 days. The use of diuretics is lower than would be expected for PDAC patients with elevated SAAG. Other therapies such as beta blockers should be investigated in this subset of patients. The etiology of ascites in these patients is poorly understood and further research is needed to establish treatment guidelines and improve outcomes.

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Section: Discussioncontrasting

confidence: 58%

Ascites Is a Poor Prognostic Factor in Advanced Pancreatic Adenocarcinoma and May Be Undertreated: A Prospective Cohort Study

Wang,

Cui,

Osipov

et al. 2024

Clin Transl Gastroenterol

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“…However, the impact of SMAD4 loss remains controversial. Several large retrospective studies have not been able to statistically demonstrate a prognostic impact of SMAD4 alterations on OS and DFS [ 10 , 52 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ]. In some studies, SMAD4 inactivation is a negative prognostic factor solely in a specific subset of patients.…”

Section: Smad4 and Pancreatic Ductal Adenocarcinomamentioning

confidence: 99%

“…In certain clinical studies, SMAD4 loss was not associated with a specific recurrence pattern. Indeed, SMAD4 deficiency did not correlate with locoregional nor distant recurrence [ 66 , 68 , 70 ].…”

Section: Smad4 and Pancreatic Ductal Adenocarcinomamentioning

confidence: 99%

The Role of SMAD4 Inactivation in Epithelial–Mesenchymal Plasticity of Pancreatic Ductal Adenocarcinoma: The Missing Link?

Racu

Lebrun

Schiavo

et al. 2022

Cancers

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Pancreatic ductal adenocarcinoma (PDAC) presents a five-year survival rate of 10% and its incidence increases over the years. It is, therefore, essential to improve our understanding of the molecular mechanisms that promote metastasis and chemoresistance in PDAC, which are the main causes of death in these patients. SMAD4 is inactivated in 50% of PDACs and its loss has been associated with worse overall survival and metastasis, although some controversy still exists. SMAD4 is the central signal transducer of the transforming growth factor-beta (TGF-beta) pathway, which is notably known to play a role in epithelial–mesenchymal transition (EMT). EMT is a biological process where epithelial cells lose their characteristics to acquire a spindle-cell phenotype and increased motility. EMT has been increasingly studied due to its potential implication in metastasis and therapy resistance. Recently, it has been suggested that cells undergo EMT transition through intermediary states, which is referred to as epithelial–mesenchymal plasticity (EMP). The intermediary states are characterized by enhanced aggressiveness and more efficient metastasis. Therefore, this review aims to summarize and analyze the current knowledge on SMAD4 loss in patients with PDAC and to investigate its potential role in EMP in order to better understand its function in PDAC carcinogenesis.

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The CXCL12-CXCR4/CXCR7 axis as a mechanism of immune resistance in gastrointestinal malignancies

Daniel

Seo

Pillarisetty

2020

Seminars in Cancer Biology

144

108

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Intratumoral Heterogeneity of SMAD4 Immunohistochemical Expression and Its Role in Prediction of Recurrence Pattern in Patients with Resectable Pancreatic Cancer

Abstract: Different areas inside primary tumor and lymph node metastases express SMAD4 heterogeneously. SMAD4 IHC expression is not a biomarker of the recurrence pattern after surgical resection for PC.

Cited by 4 publications

References 16 publications

Ascites Is a Poor Prognostic Factor in Advanced Pancreatic Adenocarcinoma and May Be Undertreated: A Prospective Cohort Study

Ascites Is a Poor Prognostic Factor in Advanced Pancreatic Adenocarcinoma and May Be Undertreated: A Prospective Cohort Study

The Role of SMAD4 Inactivation in Epithelial–Mesenchymal Plasticity of Pancreatic Ductal Adenocarcinoma: The Missing Link?

The CXCL12-CXCR4/CXCR7 axis as a mechanism of immune resistance in gastrointestinal malignancies

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