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Are ENT1/ENT1, NOTCH3, and miR-21 Reliable Prognostic Biomarkers in Patients with Resected Pancreatic Adenocarcinoma Treated with Adjuvant Gemcitabine Monotherapy?

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Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University, 500 05 Hradec Kralove, Czech Republic
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The Fingerland Department of Pathology, Faculty of Medicine and University Hospital Hradec Kralove, Charles University, 500 05 Hradec Kralove, Czech Republic
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Department of Biophysics and Physical Chemistry, Faculty of Pharmacy in Hradec Kralove, Charles University, 500 05 Hradec Kralove, Czech Republic
4
Department of Surgery, Faculty of Medicine and University Hospital Hradec Kralove, Charles University, 500 05 Hradec Kralove, Czech Republic
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(11), 1621; https://doi.org/10.3390/cancers11111621
Received: 13 September 2019 / Revised: 16 October 2019 / Accepted: 18 October 2019 / Published: 23 October 2019
Evidence on equilibrative nucleoside transporter 1 (ENT1) and microRNA-21 (miR‑21) is not yet sufficiently convincing to consider them as prognostic biomarkers for patients with pancreatic ductal adenocarcinoma (PDAC). Here, we investigated the prognostic value of ENT1/ENT1, miR-21, and neurogenic locus homolog protein 3 gene (NOTCH3) in a well-defined cohort of resected patients treated with adjuvant gemcitabine chemotherapy (n = 69). Using a combination of gene expression quantification in microdissected tissue, immunohistochemistry, and univariate/multivariate statistical analyses we did not confirm association of ENT1/ENT1 and NOTCH3 with improved disease-specific survival (DSS). Low miR-21 was associated with longer DSS in patients with negative regional lymph nodes or primary tumor at stage 1 and 2. In addition, downregulation of ENT1 was observed in PDAC of patients with high ENT1 expression in normal pancreas, whereas NOTCH3 was upregulated in PDAC of patients with low NOTCH3 levels in normal pancreas. Tumor miR‑21 was upregulated irrespective of its expression in normal pancreas. Our data confirmed that patient stratification based on expression of ENT1/ENT1 or miR‑21 is not ready to be implemented into clinical decision-making processes. We also conclude that occurrence of ENT1 and NOTCH3 deregulation in PDAC is dependent on their expression in normal pancreas. View Full-Text
Keywords: adjuvant gemcitabine monotherapy; equilibrative nucleoside transporter 1; neurogenic locus homolog protein 3; miR-21; resected pancreatic ductal adenocarcinoma; prognostic biomarker adjuvant gemcitabine monotherapy; equilibrative nucleoside transporter 1; neurogenic locus homolog protein 3; miR-21; resected pancreatic ductal adenocarcinoma; prognostic biomarker
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MDPI and ACS Style

Jiraskova, L.; Ryska, A.; Duintjer Tebbens, E.J.; Hornychova, H.; Cecka, F.; Staud, F.; Cerveny, L. Are ENT1/ENT1, NOTCH3, and miR-21 Reliable Prognostic Biomarkers in Patients with Resected Pancreatic Adenocarcinoma Treated with Adjuvant Gemcitabine Monotherapy? Cancers 2019, 11, 1621. https://doi.org/10.3390/cancers11111621

AMA Style

Jiraskova L, Ryska A, Duintjer Tebbens EJ, Hornychova H, Cecka F, Staud F, Cerveny L. Are ENT1/ENT1, NOTCH3, and miR-21 Reliable Prognostic Biomarkers in Patients with Resected Pancreatic Adenocarcinoma Treated with Adjuvant Gemcitabine Monotherapy? Cancers. 2019; 11(11):1621. https://doi.org/10.3390/cancers11111621

Chicago/Turabian Style

Jiraskova, Lucie, Ales Ryska, Erik J. Duintjer Tebbens, Helena Hornychova, Filip Cecka, Frantisek Staud, and Lukas Cerveny. 2019. "Are ENT1/ENT1, NOTCH3, and miR-21 Reliable Prognostic Biomarkers in Patients with Resected Pancreatic Adenocarcinoma Treated with Adjuvant Gemcitabine Monotherapy?" Cancers 11, no. 11: 1621. https://doi.org/10.3390/cancers11111621

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