Prognostic value of PD-L1 overexpression for pancreatic cancer: evidence from a meta-analysis

Figures & data

Table 1 Characteristics of included studies

Study	Region	Cancer type	Method	Cutoff	No of patients		Outcome	Quality score
					PD-L1 high	PD-L1 low
Birnbaum et al,^Citation23 2016	France	PC	qRT-PCR	Mean PD-L1 mRNA expression in normal pancreatic samples	87	366	OS and pathologic features	*******
Chen et al,^Citation27 2014	China	PC	IHC	Cases with >10% cells clearly stained were considered to be positive	24	39	OS and pathologic features	****
Chu et al,^Citation32 2011	China	PC	IHC	Staining score of ≥4 was considered to be positivea	37	6	Pathologic features	****
Diana et al,^Citation24 2016	UK	PDAC	IHC	Median score valueb	41	104	OS and pathologic features	****
Liu et al,^Citation28 2016	China	PC	IHC	Cases with >10% PD-L1-positive tumor cells were considered to be positive	26	20	OS	***
Loos et al,^Citation29 2008	Germany	PDAC	qRT-PCR	Median PD-L1 mRNA expression level	20	20	OS and pathologic features	***
Nomi et al,^Citation30 2007	Japan	PC	IHC	Specimens with a ≥10% PD-L1-positive tumor cells were classified as positive	20	31	OS and pathologic features	***
Wang et al,^Citation31 2010	China	PC	IHC	Specimens with >5% cells of the total tumor area stained positive were considered to be positive	40	41	OS and pathologic features	***
Wang et al,^Citation26 2017	China	PC	IHC	Staining score of ≥6 was considered to be high expressiona	27	67	OS and pathologic features	******
Yamaki et al,^Citation25 2017	Japan	PDAC	IHC	The threshold value for judging positive PID staining of PD-L1 was set to 3.0	26	16	OS and pathologic features	*****

Notes:

a PD-L1 staining scores were obtained by multiplying the staining intensities (0, negative; 1, weak; 2, medium; 3, strong) and the percentage of positive tumor (0, <5%; 1, 5%–25%; 2, 26%–50%; 3, 51%–75%; 4, >75%);

b Scoring was based on the proportion of PD-L1-positive tumor cells: 1, absent cells, 2, <25% cell density, 3, 25%–50% cell density, 4, >50% cell density.

Abbreviations: IHC, immunohistochemistry; OS, overall survival; PC, pancreatic cancer; PDAC, pancreatic ductal adenocarcinoma; PD-L1, programmed death-ligand 1; qRT-PCR, quantitative reverse transcription polymerase chain reaction.

Figure 1 Forest plot and meta-analysis of the overall survival of the PD-L1 high expression group compared with the low expression group.

Note: High PD-L1 expression was correlated with poorer overall survival in PC patients (HR: 1.76, 95% CI: 1.43–2.17, P<0.00001).
Abbreviations: df, degrees of freedom; HR, hazard ratio; IV, generic inverse variance method; PC, pancreatic cancer; PD-L1, programmed death-ligand 1; SE, standard error.

Table 2 Meta-analysis: correlation between PD-L1 overexpression and clinicopathologic characteristics

Outcomes of interest	No of studies	No of patients		RR	95% CI of RR	P-value	Study heterogeneity
		PD-L1 high	PD-L1 low				χ^2	df	I^2 (%)	P-value
Tumor status	6	188	410	1.04	0.85–1.27	0.74	16.1	5	69	0.007
Pathologic stagea	3	97	78	1.22	0.20–7.64	0.83	25.3	2	92	<0.00001
Metastatic status	4	97	152	1.40	0.88–2.23	0.16	0.27	3	0	0.97
Differentiation	6	218	406	1.57	1.25–1.98	0.0001	7.41	5	33	0.19
Lymph node metastasis	7	224	414	1.09	0.97–1.23	0.14	8.52	6	30	0.20
Vascular invasion	3	105	176	0.96	0.73–1.26	0.76	1.35	2	0	0.51
Nervous invasion	4	145	217	1.30	1.03–1.64	0.03	3.79	3	21	0.29

Notes:

a Pathologic stage = TNM stage. RR was calculated for TNM stage III–IV.

Abbreviations: df, degrees of freedom; PD-L1, programmed death-ligand 1; RR, risk ratio.

Figure 2 Subgroup analysis based on the methods used to detect PD-L1 expression.

Note: A statistical significance of the pooled HR was observed in both the subgroup with PCR method (HR: 2.24, 95% CI: 1.53–3.28, P<0.0001) and the subgroup with IHC method (HR: 1.59, 95% CI: 1.23–2.04, P=0.0003) between high and low PD-L1 expression groups.
Abbreviations: df, degrees of freedom; HR, hazard ratio; IHC, immunohistochemistry; IV, generic inverse variance method; PCR, polymerase chain reaction; PD-L1, programmed death-ligand 1; SE, standard error.

Figure 3 Funnel plot illustrating the meta-analysis of the overall survival.

Note: There was no obvious publication bias.
Abbreviations: IHC, immunohistochemistry; PCR, polymerase chain reaction; SE, standard error.

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