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Meta-Analysis
. 2023 Apr 17:14:1119168.
doi: 10.3389/fimmu.2023.1119168. eCollection 2023.

Prognostic value of programmed cell death ligand 1 expression in patients with intrahepatic cholangiocarcinoma: a meta-analysis

Feng Xian  1   2 , Dacheng Ren  2 , Jun Bie  2 , Guohui Xu  3
Affiliations
Meta-Analysis

Prognostic value of programmed cell death ligand 1 expression in patients with intrahepatic cholangiocarcinoma: a meta-analysis

Feng Xian et al. Front Immunol. .

Abstract

Background: Programmed cell death ligand 1 (PD-L1) is highly expressed in intrahepatic cholangiocarcinoma (ICC) tissues. But there is still a dispute over the prognostic value of PD-L1 in patients with ICC. This study aimed to evaluate the prognostic value of PD-L1 expression in patients with ICC.

Methods: We performed a meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines. We searched the literature from PubMed, Embase, Web of Science, and the Cochrane Library up to December 5, 2022. Hazard ratios (HR) and their 95% confidence intervals (95% CI) were calculated to analyze the overall survival (OS), recurrence-free survival (RFS), and time to relapse. The quality of the studies was assessed using the Newcastle-Ottawa scale. Publication bias was assessed using a funnel plot and Egger's test.

Results: Ten trials with 1944 cases were included in this meta-analysis. The results showed that the low-PD-L1 group had a statistically significant advantage in OS (HR, 1.57; 95% CI, 1.38-1.79, P <0.00001), RFS (HR, 1.62; 95% CI, 1.34-1.97, P <0.00001), and time to relapse (HR, 1.60; 95% CI, 1.25-2.05, P = 0.0002) compared with the high-PD-L1 group. High programmed cell death (PD1)levels, on the other hand, were correlated with poorer OS (HR, 1.96; 95% CI, 1.43-2.70; P <0.0001) and RFS (HR, 1.87; 95% CI, 1.21-2.91; P = 0.005). Multivariate analysis showed that PD-L1 could act as an independent predictor for OS (HR, 1.48; 95% CI, 1.14-1.91; P = 0.003) and RFS (HR, 1.74; 95% CI, 1.22-2.47; P = 0.002), and PD1 acted as an independent predictor for OS (HR, 1.66; 95% CI, 1.15-2.38; P = 0.006).

Conclusion: This meta-analysis demonstrated that high PD-L1/PD1 expression is associated with poor survival in ICC. PD-L1/PD1 may be a valuable prognostic and predictive biomarker and potential therapeutic target in ICC.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022380093.

Keywords: intrahepatic carcinoma; meta-analysis; prognostic value; programmed cell death 1 (PD-1); programmed cell death ligand 1 (PDL1).

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram of study selection.
Figure 2
Figure 2
A forest plot of OS between low- and high-PD-L1 expression: (A) pooled OS by univariate analysis; (B) pooled OS by multivariate analysis. A forest plot of OS between low- and high-PD1 expression: (C) pooled OS by univariate analysis; (D) pooled OS by multivariate analysis.PD-L1, programmed cell death ligand 1; OS, overall survival; SE, standard error.
Figure 3
Figure 3
A forest plot of RFS between low- and high-PD-L1 expression: (A) pooled RFS in univariate analysis; (B) pooled RFS in multivariate analysis. A forest plot of RFS between low- and high-PD1 expression: (C) pooled RFS in univariate analysis; (D) pooled RFS in multivariate analysis. RFS, recurrence-free survival; PD-L1, programmed cell death ligand 1; SE, standard error.
Figure 4
Figure 4
A forest plot of time to relapse between low- and high-PD-L1 expression. PD-L1, programmed cell death ligand 1; SE, standard error.
Figure 5
Figure 5
The subgroup analyses for PD-L1 expression related OS and RFS. (A) the subgroup analyses for PD-L1 expression related OS based on different cut-offs, (B) the subgroup analyses for PD-L1 expression related OS based on different scoring methods, (C) the subgroup analyses for PD-L1 expression related RFS based on cut-offs. NR, not reported.
Figure 6
Figure 6
Sensitivity analysis of the meta-analysis: (A) OS in PD-L1 expression; (B) RFS in PD-L1 expression; (C) TTR in PD-L1 expression; (D) OS in PD1 expression; (E) RFS in PD1 expression. PD-L1, programmed cell death ligand 1; OS, overall survival; RFS, recurrence-free survival.
Figure 7
Figure 7
Funnel plot of the meta-analysis: (A) OS in PD-L1 expression; (B) RFS in PD-L1 expression; (C) TTR in PD-L1 expression; (D) OS in PD1 expression; (E) RFS in PD1 expression. PD-L1, programmed cell death ligand 1; OS, overall survival; RFS, recurrence-free survival; TTR, time to relapse.
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