Shaojie Xu,Yiming Feng,Xingyin Li,Zaozao Huang,Hewei Li,Ganxin Wang. Prognostic role of plasma levels of γ-glutamyl transpeptidase in patients with advanced gastric cancer treated with anti-PD-1 immunotherapy. Oncol Transl Med, 2022, 8: 109-153.
Prognostic role of plasma levels of γ-glutamyl transpeptidase in patients with advanced gastric cancer treated with anti-PD-1 immunotherapy
Received:December 31, 2021  Revised:June 14, 2022
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KeyWord:gastric cancer; programmed cell death receptor 1; γ-glutamyl transpeptidase (GGT); prognosis
Author NameAffiliationE-mail
Shaojie Xu Huazhong University of Science and Technology u201712199@hust.edu.cn 
Yiming Feng Union Hospital, Tongji Medical College, Huazhong University of Science and Technology  
Xingyin Li Huazhong University of Science and Technology  
Zaozao Huang Yangchunhu Community Hospital, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology huangzaozao1986@163.com 
Hewei Li Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology  
Ganxin Wang Union Hospital, Tongji Medical College, Huazhong University of Science and Technology  
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Abstract:
      Objective Antibodies targeting programmed cell death protein 1 (PD-1) have become the mainstay of treatment for chemotherapy-refractory gastric cancer, characterized by high levels of programmed cell death ligand-1 (PDL-1) expression. However, the routine clinical implementation of PDL-1 testing is currently limited by the lack of robust detection methods. In this regard, the role of plasma γ-glutamyl transpeptidase (GGT), an N-terminal nucleophilic hydrolase, as an independent predictor of the efficacy of anti-PD-1 therapy remains unknown. In this study, we aimed to assessed the prognostic role of changes in plasma GGT levels (6 weeks vs. baseline) in patients with advanced gastric cancer treated with anti-PD-1 immunotherapy. Methods We retrospectively analyzed data from 57 patients with gastric cancer treated with anti-PD-1 antibodies (camrelizumab, sintilimab, nivolumab, tislelizumab, and toripalimab) at the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, from July 2018 to February 2021. Results We found that after 6 weeks of treatment, there were significant differences between responders and non-responders with respect to plasma GGT levels (P < 0.001). Multivariate logistic regression analysis revealed that the continuous value of the 6-week difference in GGT levels (OR = 1.437, 95% CI = 1.116– 1.849, P = 0.005) and 6-week difference in GGT ≥ 0 or < 0 (OR = 53.675, 95% CI = 6.379–451.669, P < 0.001) were independent predictors of disease control. Survival analysis indicated that a reduction in plasma GGT6 levels during treatment was significantly associated with a favorable progression-free survival (PFS) and overall survival (P < 0.001). Consistently, univariate and multivariate Cox regression analyses revealed that a reduction in plasma GGT6 levels during treatment was an independent predictor of PFS (HR = 1.033, 95% CI = 1.013–1.053, P = 0.001). Conclusion Alterations in plasma GGT levels during treatment can be used as a predictor of disease progression and survival in patients with advanced gastric cancer undergoing treatment with anti-PD-1 antibodies.
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