The prognostic role of soluble transforming growth factor‐β and its correlation with soluble programmed death‐ligand 1 in biliary tract cancer

2020 ◽  
Author(s):  
Jin Won Kim ◽  
Kyung‐Hun Lee ◽  
Ji‐Won Kim ◽  
Koung Jin Suh ◽  
Ah‐Rong Nam ◽  
...  
Keyword(s):  
Growth Factor ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Prognostic Role ◽  
Programmed Death Ligand 1 ◽  
Tract Cancer ◽  
Programmed Death

The prognostic role of soluble transforming growth factor-β (sTGFb) and soluble programmed death-ligand 1 (sPDL1) in biliary tract cancer patients treated with binimetinib and capecitabine.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 257-257
Author(s):  
Jin Won Kim ◽  
Kyung-Hun Lee ◽  
Ji-Won Kim ◽  
Koung Jin Suh ◽  
Ah-Rong Nam ◽  
...  
Keyword(s):  
Growth Factor ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Transforming Growth Factor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Prognostic Role ◽  
Programmed Death Ligand 1 ◽  
Positive Correlation ◽  
Tract Cancer ◽  
Programmed Death

257 Background: Transforming growth factor (TGF) -β signaling is important for tumor growth and metastasis in biliary tract cancer (BTC). TGF-β attenuates tumor response to programmed death-ligand 1 (PD-L1) blockade. This study aimed to evaluate a correlation between soluble TGF-β (s TGF-β) and soluble PD-L1 (sPD-L1) and its prognostic role in BTC. Methods: Study population consisted of 34 patients enrolled in phase Ib clinical trial of binimetinib (MEK inhibitor) with capecitabine in gemcitabine-pretreated BTC (ClinicalTrials.gov: NCT02773459). Blood samples at screening, after first cycle, after second cycle, and at disease progression were prospectively collected. Plasma sTGF-β and sPD-L1 values were measured by using an enzyme-linked immunosorbent assay. Results: In total 34 patients, 25 (73.5%) and 9 patients (26.5%) were second-line and third-line setting, respectively. Median progression-free survival (PFS) and overall survival (OS) were 4.1 and 7.8 months. The mean baseline sTGF-β and sPD-L1 were 18.7 ng/ml and 3.1 ng/ml. There was a positive correlation between sTGF-β and sPD-L1 value (pearson correlation = 0.596, p < 0.001). Mean baseline value was likely to be higher in best response of progressive disease, followed by stable disease and partial response. Similarly, higher baseline sTGF-β showed significantly shorter PFS (3.4 vs 5.1 months (m), p = 0.047) and OS (5.4 vs 9.7 m, p = 0.042). Higher baseline sPD-L1 also had a trend for poor PFS and OS (PFS: 3.0 vs 4.3 m, p = 0.220; OS: 6.4 vs 9.7 m, p = 0.140). Regarding changes from baseline to after first cycle, sTGF-β change of > 3.6 ng/ml demonstrated significantly shorter OS (5.9 vs 10.8 m, p = 0.020), although PFS did not differ according to sTGF-β change (p = 0.210). In contrast, OS did not differ according to sPD-L1 change (p = 0.190). sPD-L1 change > -1.7 ng/ml even had longer PFS (5.1 vs 2.2 m, p = 0.005). Conclusions: In BTC patients with binimetinib and capecitabine, there is a positive correlation between sTGF-β and sPD-L1 value and higher baseline sTGF-β and sPD-L1 indicate a worse prognosis. The early change of sTGF-β and sPD-L1 during treatment could predict the survival.

scholarly journals Prognostic role of programmed death-ligand 1 expression in patients with biliary tract cancer: a meta-analysis

Aging ◽  
2019 ◽  
Vol 11 (24) ◽  
pp. 12568-12580
Author(s):  
Changjiang Lei ◽  
Xiulan Peng ◽  
Xiaojun Gong ◽  
Ying Fan ◽  
Shenglin Wu ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Meta Analysis ◽  
Prognostic Role ◽  
Programmed Death Ligand 1 ◽  
Tract Cancer ◽  
Programmed Death

The prognostic role of soluble transforming growth factor-β related with soluble programmed death-ligand 1 in biliary tract cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4094-4094
Author(s):  
Jin Won Kim ◽  
Hyerim Ha ◽  
Kyung-Hun Lee ◽  
Ah-Rong Nam ◽  
Ju-Hee Bang ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Transforming Growth Factor ◽  
Pearson Correlation ◽  
Positive Association ◽  
Prognostic Role ◽  
Programmed Death Ligand 1 ◽  
Tract Cancer ◽  
Programmed Death ◽  
Baseline Levels ◽  
Worse Prognosis

4094 Background: We previously reported that soluble programmed death-Ligand 1 (sPD-L1) at pre-chemotherapy indicated the prognostic value for overall survival (OS) and the dynamics of sPD-L1 during palliative chemotherapy correlated with disease burden in biliary tract cancer (BTC). Transforming growth factor (TGF) -β attenuates tumor response to PD1/PD-L1 inhibitors. Strategy of dual targeting of PD1/PD-L1 and TGF-β is now under investigation. This study aimed to evaluate the association between soluble TGF-β (sTGF-β) and sPD-L1, dynamics during chemotherapy and its prognostic role in BTC. Methods: Study population consisted of 90 BTC patients treated with first line chemotherapy. Blood samples at pre-and post-chemotherapy and at disease progression (PD) were prospectively collected. Plasma sTGF-β and sPD-L1 levels were measured by using an enzyme-linked immunosorbent assay. Results: The median progression free survival (PFS) and OS of all patients was 6.9 months (m) (95% CI, 5.2-8.6) and 11.5 m (95% CI, 9.4-13.6). The best response was CR in 7 (7.8%), PR in 20 (22.2%), SD in 52 (57.8%), and PD in 11 patients (12.2%). The mean baseline sTGF-β and sPD-L1 were 16.4 ng/ml and 1.3 ng/ml. There was a positive association between sTGF-β and sPD-L1 in terms of baseline levels and changes after chemotherapy (at pre-chemo, Pearson correlation = 0.578, p < 0.001; change after chemotherapy, Pearson correlation = 0.542, p < 0.001). Patients with higher pre-chemotherapy sPD-L1 ( > 1.3 ng/ml) showed worse OS (9.2 vs 16.2 m, p < 0.001). Both sPD-L1 (1.8 vs 1.0 ng/ml, p < 0.001) and sTGF-β (20.5 vs 11.6 ng/ml, p < 0.001) were increased significantly at the time of PD compared with pre-chemotherapy. Regarding changes after chemotherapy, increased sTGF-β after chemotherapy (Δ > 3.2 ng/ml) had worse prognosis (PFS: 5.1 vs 7.3 m, p = 0.024; OS: 9.2 vs 12.3 m, p = 0.028). This prognostic value of change of sTGF-β after chemotherapy was also significant in multivariable analysis with other clinical factors (PFS: HR = 1.78, p = 0.022; OS: HR = 1.86, p = 0.018). Conclusions: In BTC, there is a positive association between sTGF-β and sPD-L1 value in terms of baseline levels and changes after chemotherapy. sTGF-β could be associated with the survival, particularly, increased value after chemotherapy indicates worse prognosis.

scholarly journals Restoration of RUNX3 enhances transforming growth factor-?-dependent p21 expression in a biliary tract cancer cell line

2007 ◽  
Vol 98 (6) ◽  
pp. 838-843 ◽  
Author(s):  
Kazunori Hasegawa ◽  
Shujiro Yazumi ◽  
Manabu Wada ◽  
Toshiharu Sakurai ◽  
Masaya Kida ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Line ◽  
Cancer Cell ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Transforming Growth Factor ◽  
Cancer Cell Line ◽  
Tract Cancer
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