TY - JOUR
T1 - It Takes Two to Tango
T2 - Potential Prognostic Impact of Circulating TGF-Beta and PD-L1 in Pancreatic Cancer
AU - Garajová, Ingrid
AU - Cavazzoni, Andrea
AU - Verze, Michela
AU - Minari, Roberta
AU - Pedrazzi, Giuseppe
AU - Balsano, Rita
AU - Gelsomino, Fabio
AU - Dalla Valle, Raffaele
AU - Digiacomo, Graziana
AU - Giovannetti, Elisa
AU - Leonardi, Francesco
N1 - Funding Information: Funding: This research was funded by the Bennink Foundation, Italian Association for Cancer Research, Italy, and Fondazione Pisa per la Scienza, 56017 San Giuliano Terme (PI), Italy (to E.G.). Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/7/1
Y1 - 2022/7/1
N2 - Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly devastating disease with rising incidence and poor prognosis. The lack of reliable prognostic biomarkers hampers the individual evaluation of the survival and recurrence potential. Methods: Here, we investigate the value of plasma levels of two potential key players in molecular mechanisms underlying PDAC aggressiveness and immune evasion, soluble TGF-beta (sTGF-beta) and sPD-L1, in both metastatic and radically-resected PDAC. To this aim we prospectively enrolled 38 PDAC patients and performed appropriate statistical analyses in order to evaluate their correlation, and role in the prediction of disease relapse/progression, and patients’ outcome. Results: Metastatic patients showed lower levels of circulating sTGF-beta and higher levels of sPD-L1 compared to radically-resected patients. Moreover, a decrease in sTGF-beta levels (but not sPD-L1) was significantly associated with disease relapse in radically-resected patients. We also observed lower sTGF-beta at disease progression after first-line chemotherapy in metastatic patients, though this change was not statistically significant. We found a significant correlation between the levels of sTGF-beta and sPD-L1 before first-line chemotherapy. Conclusions: These findings support the possible interaction of TGF-beta and PD-L1 pathways and suggest that sTGF-beta and sPD-L1 might synergize and be new potential blood-based biomarkers.
AB - Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly devastating disease with rising incidence and poor prognosis. The lack of reliable prognostic biomarkers hampers the individual evaluation of the survival and recurrence potential. Methods: Here, we investigate the value of plasma levels of two potential key players in molecular mechanisms underlying PDAC aggressiveness and immune evasion, soluble TGF-beta (sTGF-beta) and sPD-L1, in both metastatic and radically-resected PDAC. To this aim we prospectively enrolled 38 PDAC patients and performed appropriate statistical analyses in order to evaluate their correlation, and role in the prediction of disease relapse/progression, and patients’ outcome. Results: Metastatic patients showed lower levels of circulating sTGF-beta and higher levels of sPD-L1 compared to radically-resected patients. Moreover, a decrease in sTGF-beta levels (but not sPD-L1) was significantly associated with disease relapse in radically-resected patients. We also observed lower sTGF-beta at disease progression after first-line chemotherapy in metastatic patients, though this change was not statistically significant. We found a significant correlation between the levels of sTGF-beta and sPD-L1 before first-line chemotherapy. Conclusions: These findings support the possible interaction of TGF-beta and PD-L1 pathways and suggest that sTGF-beta and sPD-L1 might synergize and be new potential blood-based biomarkers.
KW - liquid biopsy
KW - pancreatic adenocarcinoma
KW - prognostic biomarker
KW - sPD-L1
KW - sTGF-beta
UR - http://www.scopus.com/inward/record.url?scp=85133333549&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/life12070960
DO - https://doi.org/10.3390/life12070960
M3 - Article
C2 - 35888050
SN - 2075-1729
VL - 12
JO - Life
JF - Life
IS - 7
M1 - 960
ER -