TY - JOUR
T1 - Prognostic role of high-grade tumor budding in pancreatic ductal adenocarcinoma
T2 - A systematic review and meta-analysis with a focus on epithelial to mesenchymal transition
AU - Lawlor, Rita T.
AU - Veronese, Nicola
AU - Nottegar, Alessia
AU - Malleo, Giuseppe
AU - Smith, Lee
AU - Demurtas, Jacopo
AU - Cheng, Liang
AU - Wood, Laura D.
AU - Silvestris, Nicola
AU - Salvia, Roberto
AU - Scarpa, Aldo
AU - Luchini, Claudio
N1 - Funding Information:
This work has been supported by Associazione Italiana Ricerca Cancro (AIRC) grant no. 12182 (A.S.), European Community Transcan Programme: Bio-PaC (R.T.L. and A.S.) and FP7 European Community Grant Cam-Pac (no. 602783) (R.T.L. and A.S.). The funding agencies had no role in the collection, analysis and interpretation of data, and in the writing of the manuscript.
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - This study aims at clarifying the prognostic role of high-grade tumor budding (TB) in pancreatic ductal adenocarcinoma (PDAC) with the first systematic review and meta-analysis on this topic. Furthermore, we analyzed with a systematic review the relationship between TB and a recently suggested TB-associated mechanism: the epithelial to mesenchymal transition (EMT). Analyzing a total of 613 patients, 251 of them (40.9%) with high grade-TB, we found an increased risk of all-cause mortality (RR, 1.46; 95% CI, 1.13-1.88, p = 0.004; HR, 2.65; 95% CI, 1.79-3.91; p < 0.0001) and of recurrence (RR, 1.61; 95% CI, 1.05-2.47, p = 0.03) for PDAC patients with high-grade TB. Moreover, we found that EMT is a central process in determining the presence of TB in PDAC. Thanks to this meta-analysis, we demonstrate the potential clinical significance of high-grade TB for prognostic stratification of PDAC. TB also shows a clear association with the process of EMT. Based on the results of the present study, TB should be conveyed in pathology reports and taken into account by future oncologic staging systems.
AB - This study aims at clarifying the prognostic role of high-grade tumor budding (TB) in pancreatic ductal adenocarcinoma (PDAC) with the first systematic review and meta-analysis on this topic. Furthermore, we analyzed with a systematic review the relationship between TB and a recently suggested TB-associated mechanism: the epithelial to mesenchymal transition (EMT). Analyzing a total of 613 patients, 251 of them (40.9%) with high grade-TB, we found an increased risk of all-cause mortality (RR, 1.46; 95% CI, 1.13-1.88, p = 0.004; HR, 2.65; 95% CI, 1.79-3.91; p < 0.0001) and of recurrence (RR, 1.61; 95% CI, 1.05-2.47, p = 0.03) for PDAC patients with high-grade TB. Moreover, we found that EMT is a central process in determining the presence of TB in PDAC. Thanks to this meta-analysis, we demonstrate the potential clinical significance of high-grade TB for prognostic stratification of PDAC. TB also shows a clear association with the process of EMT. Based on the results of the present study, TB should be conveyed in pathology reports and taken into account by future oncologic staging systems.
KW - Budding
KW - Buds
KW - EMT
KW - Epithelial to mesenchymal transition
KW - Pancreatic cancer
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U2 - 10.3390/cancers11010113
DO - 10.3390/cancers11010113
M3 - Review article
C2 - 30669452
AN - SCOPUS:85061985339
VL - 11
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 1
M1 - 113
ER -