The clinicopathological and prognostic significance of PD-L1 expression in gastric cancer: a meta-analysis of 10 studies with 1,901 patients.
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SUBMITTER: Zhang M
PROVIDER: S-EPMC5124943 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PurposeTo systematically evaluate the correlation between PD-L1 expression and clinicopathological features and prognosis of colorectal cancer (CRC).MethodsSeven databases (PubMed, Cochrane Library, EMBASE, Web of Science, CBM, Wanfang, and CNKI) were searched through May 2020. Risk of bias and quality of evidence were assessed by using the Newcastle-Ottawa scale (NOS), and meta-analysis was carried out by using the Review Manager 5.3 software on the studies with the quality evaluation scores ??6. Meta-regression analysis was used to determine the independent role of PD-L1 expression on CRC prognosis after adjusting clinicopathological features and treatment methods.ResultsA total of 8823 CRC patients in 32 eligible studies. PD-L1 expression was correlated with lymphatic metastasis (yes/no; OR?=?1.24, 95% CI (1.11, 1.38)), diameter of tumor (??5 cm/<?5 cm; OR?=?1.34, 95% CI (1.06, 1.70)), differentiation (high-middle/low; OR?=?0.68, 95% CI (0.53, 0.87)), and vascular invasion (yes/no; OR?=?0.80, 95% CI (0.69, 0.92)). PD-L1 expression shortened the overall survival (hazard ratio (HR) =?1.93, 95% CI (1.66, 2.25)), disease-free survival (HR?=?1.76, 95% CI (1.50, 2.07)), and progression-free survival (HR?=?1.93, 95% CI (1.55, 2.41)). Meta-regression showed that PD-L1 expression played a significant role on poor CRC OS (HR?=?1.95, 95% CI (1.92, 3.98)) and disease-free survival (HR?=?2.14, 95% CI (0.73, 4.52)).ConclusionPD-L1 expression independently predicted a poor prognosis of CRC.
| S-EPMC7782388 | biostudies-literature
Project description:ObjectiveTo analyze the prognostic value of programmed death factor ligand 1 (PD-L1) in colorectal cancer.MethodsElectronic databases, such as PubMed, Web of Science, Embase, and Cochrane library, were searched to identify studies evaluating the PD-L1 expression and overall survival (OS) in these patients. Afterwards, the relevant data were extracted to perform the meta-analysis.ResultsA total of 3481 patients were included in 10 studies. The combined hazard ratio (HR) was 1.22 (95%CI = 1.01-1.48, P = 0.04), indicating that high expression of PD-L1 was significantly correlated with poor prognosis of colorectal cancer. Apropos of clinicopathological features, the merged odds ratio (OR) exhibited that highly expressed PD-L1 was firmly related to lymphatic invasion (OR = 3.49, 95%CI = 1.54-7.90, P = 0.003) and advanced stage (OR = 1.77, 95%CI = 1.41-2.23, P < 0.00001), but not correlative with patients' gender, microsatellite instability, or tumor location.ConclusionThe expression of PD-L1 can be utilized as an independent factor in judging the prognosis of colorectal cancer, and patients with advanced cancer or lymphatic invasion are more likely to express PD-L1. This conclusion may lay a theoretical foundation for the application of PD-1/PD-L1 immunoassay point inhibitors but still needs verifying by sizeable well-designed cohort studies.
| S-EPMC6320581 | biostudies-literature
Project description:Background: Recently, blockade of immune checkpoint has emerged as one of the most potential treatments for solid tumors. Programmed cell death ligand 1(PD-L1), a member of the B7 family of molecules, plays a crucial role in tumor immunobiology. However, the prognostic significance of PD-L1 in cholangiocarcinoma (CCA) patients remains controversial. This study aimed to inquire into the prognostic and clinicopathological significance of PD-L1 in CCA via a meta-analysis. Methods: We searched PubMed, the Cochrane Library, Embase, Web of Science and Google Scholar up to April 2019, regardless of the region or language, for studies on the correlation between clinicopathology/prognosis and PD-L1 in patients with CCA. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to investigate the prognostic significance of PD-L1 expression in cholangiocarcinoma. The odds ratios (ORs) were also determined to explore the association between PD-L1 expression and clinicopathological features. Results: Our meta-analysis included 11 studies with 1,066 patients. The meta-analysis of these studies indicated a trend that high PD-L1 expression indicated a poor OS, but the result was not statistically significant (HR = 1.62, 95% CI [0.98-2.68], p = 0.063). For DFS, although the pooled result is not statistically significant, it trends toward being significant that high PD-L1 expression indicated improved DFS (HR = 0.80, 95% CI [0.62, 1.04], p = 0.092). In subgroup analyses, the results were not consistent across the subgroups that were divided based on the publication year (before 2018: HR = 1.92, 95% CI [1.34-2.75], p < 0.001; after 2018: HR = 1.42, 95% CI [0.70-2.89], p = 0.335). Moreover, PD-L1 expression in TCs significantly correlated with the AJCC TNM stage of CCA (OR = 0.52, 95% CI [0.27, 0.99], p = 0.09). Conclusion: Our meta-analyses revealed that PD-L1 expressed in TCs was significantly correlated with the AJCC TNM stage of CCA. Based on the included studies, we found that PD-L1 indeed expressed in both TCs and ICs in CCA patients, raising the possibility of the use of anti-PD-1/PD-L1 therapy for CCA patients. In contrast, expression of PD-L1 did not seem to be associated with patient outcome in our study. The prognostic role of PD-L1 in CCA demands further investigation.
| S-EPMC6759577 | biostudies-literature
Project description:A large number of studies have shown that programmed death-ligand 1 (PD-L1) is abnormally expressed in gliomas. However, the prognostic significance of PD-L1 expression in glioma patients remains unresolved. Accordingly, we conducted a meta-analysis to determine the prognostic role of high PD-L1 in patients with glioma. Electronic databases were searched to identify studies evaluating PD-L1 expression and overall survival (OS) in these patients. A total of 6 studies (published in 4 articles) that involved 1052 patients were included. Pooled results showed that high PD-L1 expression was associated with worse OS in glioma patients (HR?=?1.30, 95% CI: 1.02-1.65, P?=?0.032). Further subgroup analysis indicated that high PD-L1 expression in glioblastoma (GBM) was also associated with worse OS (HR?=?1.40, 95% CI: 1.03-1.90, P?=?0.030). Conversely, in index subgroup analysis, neither PD-L1 protein (HR?=?1.43, 95% CI: 0.97-2.10, P?=?0.068) nor gene (HR?=?1.20, 95% CI: 0.83-1.74, P?=?0.322) expression was significantly associated with OS. PD-L1 may represent a promising biomarker that predicts disease progression in patients with glioma or GBM. However, because of our limited sample size, further prospective or retrospective multi-centre, well-designed studies should be performed to verify this result.
| S-EPMC5484664 | biostudies-literature
Project description:BackgroundThe clinicopathological and prognostic significance of SRY-box transcription factor 9 (SOX9) expression in gastric cancer (GC) patients is still controversial. Our aim is to investigate the clinicopathological and prognostic value of SOX9 expression in GC patients.MethodsA systemic literature search and meta-analysis were used to evaluate the clinicopathological significance and overall survival (OS) of SOX9 expression in GC patients. The Cancer Genome Atlas (TCGA) dataset was used to investigate the relationship between SOX9 expression and OS of stomach adenocarcinoma (STAD) patients.ResultsA total of 11 articles involving 3,060 GC patients were included. In GC patients, the SOX9 expression was not associated with age [odds ratio (OR) = 0.743, 95% CI = 0.507-1.089, p = 0.128], sex (OR = 0.794, 95% CI = 0.605-1.042, p = 0.097), differentiation (OR = 0.728, 95% CI = 0.475-1.115, p = 0.144), and lymph node metastasis (OR = 1.031, 95% CI = 0.793-1.340, p = 0.820). SOX9 expression was associated with depth of invasion (OR = 0.348, 95% CI = 0.247-0.489, p = 0.000) and TNM stage (OR = 0.428, 95% CI = 0.308-0.595, p = 0.000). The 1-year OS (OR = 1.507, 95% CI = 1.167-1.945, p = 0.002), 3-year OS (OR = 1.482, 95% CI = 1.189-1.847, p = 0.000), and 5-year OS (OR = 1.487, 95% CI = 1.187-1.862, p = 0.001) were significantly shorter in GC patients with high SOX9 expression. TCGA analysis showed that SOX9 was upregulated in STAD patients compared with that in normal patients (p < 0.001), and the OS of STAD patients with a high expression of SOX9 is poorer than that in patients with low expression of SOX9, but the statistical difference is not obvious (p = 0.31).ConclusionSOX9 expression was associated with the depth of tumor invasion, TNM stage, and poor OS of GC patients. SOX9 may be a potential prognostic factor for GC patients but needs further study.Systematic review registrationPROSPERO, ID NUMBER 275712.
| S-EPMC8458960 | biostudies-literature
Project description:Background: A series of studies have explored the prognostic value of programmed death-ligand 1 (PD-L1) in patients with endometrial cancer (EC); however, the results are controversial. Therefore, this meta-analysis was performed to estimate the associations between PD-L1 expression and the prognosis and clinicopathological features of EC. Methods: A comprehensive literature search of PubMed, Web of Science, and Embase was conducted up until September 06, 2019. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS) were computed using the random-effects model (REM) or fixed-effects model (FEM). Odds ratios (ORs) and 95% CIs were calculated to evaluate the relationship between PD-L1 and clinicopathological factors. Results: A total of 9 studies with 1,615 patients were included in the meta-analysis. The combined data showed that high expression of PD-L1 was not significantly correlated with OS (HR = 1.20, 95% CI = 0.41-3.52, p = 0.737) or PFS (HR = 1.12, 95% CI = 0.50-2.54, p = 0.778) in EC. In addition, PD-L1 expression was significantly associated with poor differentiation (OR = 2.82, 95% CI = 1.96-4.06, P < 0.001) and advanced stage (OR = 1.71, 95% CI = 1.12-2.60, p = 0.013). Conclusion: This meta-analysis suggests that PD-L1 expression is not associated with poor prognosis in patients with EC. However, PD-L1 expression is positively correlated with poor differentiation and advanced tumor stage in EC.
| S-EPMC7203339 | biostudies-literature
Project description:BACKGROUND:Immunohistochemistry (IHC) for programmed cell death ligand 1 (PD-L1) displays staining diversity. We compared IHC staining of PD-L1 in gastric cancer (GC) by using three commercially available antibody clones, and analyzed the correlation with the prognosis. METHODS:IHC using PD-L1 antibodies (clones SP142, 28-8 and E1L3N) in 315 formalin-fixed paraffin-embedded samples was qualitatively compared at the 1, 5 and 10% cut-off by two pathologists on total, tumor and immune/stromal cells. We used computer - assisted scoring to quantitatively analyze and compare the "H-score" of PD-L1 expression in 66 samples on total cells. The antibody clone SP142 was selected to investigate the infiltration of PD-L1+CD8+ T cells using automated quantitative immunofluorescence analyses (n?=?50) and the prognostic significance. The prognoses were assessed by log-rank test. RESULTS:PD-L1 clones SP142 and 28-8 displayed great concordance by qualitative (??=?0.816, 0.810 for total cells and tumor cells at the 5% cut-off) and quantitative analyses (R2?=?0.7991, 0.8187 for positive percentage and "H-score"). PD-L1 clone SP142 showed the highest positivity in immune/stromal cells staining (18.41%) compared to 28-8 (7.62%), while clone E1L3N showed poor staining in both tumor and immune/stromal cells. Clone SP142, but not 28-8 and E1L3N, predicted a worse prognosis at the 5% cut-off (p?=?0.0243). Both the clone SP142 and 28-8 had high inter-pathologist correlation for tumor staining (R2?=?0.9805 and R2?=?0.9853), but a moderate correlation for stromal/immune cell staining (R2?=?0.5653 and R2?=?0.5745). Furthermore, a higher density of PD-L1+CD8+ T cells was correlated with a shorter survival time (R2?=?0.0909, p?=?0.0352). CONCLUSIONS:PD-L1 antibody clone SP142 was superior in cell staining, particularly in immune/stromal cell and prognosis. These findings are important for selection of PD-L1 antibody clones in the future diagnostic test.
| S-EPMC6249875 | biostudies-literature
Project description:The advent of checkpoint immunotherapy, particularly with programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors, has provided ground-breaking results in several advanced cancers. Substantial efforts are being made to extend these promising therapies to other refractory cancers such as gliomas, especially glioblastoma, which represents the most frequent and malignant glioma and carries an exceptionally grim prognosis. Thus, there is a need for new therapeutic strategies with related biomarkers. Gliomas have a profoundly immunosuppressive tumour micro-environment and evade immunological destruction by several mechanisms, one being the expression of inhibitory immune checkpoint molecules such as PD-L1. PD-L1 is recognised as an important therapeutic target and its expression has been shown to hold prognostic value in different cancers. Several clinical trials have been launched and some already completed, but PD-1/PD-L1 inhibitors have yet to show convincing clinical efficacy in gliomas. Part of the explanation may reside in the vast molecular heterogeneity of gliomas and a complex interplay within the tumour micro-environment. In parallel, critical knowledge about PD-L1 expression is beginning to accumulate including knowledge on expression levels, testing methodology, co-expression with other checkpoint molecules and prognostic and predictive value. This article reviews these aspects and points out areas where biomarker research is needed to develop more successful checkpoint-related therapeutic strategies in gliomas.
| S-EPMC9298327 | biostudies-literature
Project description:BackgroundHigh mobility group protein A2 (HMGA2) overexpression has been reported to be closely related to tumor progression [1-4] and indicate significantly worse overall survival in gastric cancer [5-8]. However, a final consensus regarding this issue has not yet been reached. Thus, we conducted a meta-analysis to evaluate the association between HMGA2 expression and prognosis of gastric cancer patients.MethodsThe Cochrane Library, Embase, PubMed, Web of Science and China Biology Medicine databases were searched to identify eligible literature published prior to September 2016. In the included studies, the level of HMGA2 amplification was evaluated by immunohistochemistry. We performed a meta-analysis, and pooled relative risk (RRs), hazard ratio (HRs), and 95% confidence intervals (CIs) were analyzed using Review Manager 5.3.ResultsSix studies [5-7, 9-11] involving 712 gastric cancer patients were included and stratified by HMGA2 amplification magnitude. The results of the analysis indicated that higher HMGA2 levels were associated with several clinicopathological parameters and predicted poor prognosis in terms of overall survival (OS).ConclusionsThe results of the present study indicate that higher HMGA2 levels were significantly associated with TNM stage, lymph node status, vascular invasion, and poor OS in patients with gastric cancer. In conclusion, HMGA2 may serve as a promising prognostic biomarker in gastric cancer.
| S-EPMC5725036 | biostudies-literature
Project description:BackgroundAn increasing number of studies have examined the ability of programmed death-ligand 1 (PD-L1) to function as a marker for tumor prognosis. However, whether PD-L1 expression is a prognostic factor for the poor outcomes in many human cancers remains controversial. This study aims to investigate the prognostic role of PD-L1 expression through a meta-analysis update of 60 studies.MethodsThe studies were identified by searching PubMed, Embase, Google Scholar, and Cochrane Library, and were assessed by further quality evaluation. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for total and stratified analyses were calculated to investigate the association between the PD-L1 expression and the overall (OS) and disease-free (DFS) or progression-free survivals (PFS) of cancer patients. Heterogeneity and publication bias were also investigated.ResultsThe results indicated that PD-L1 overexpression can predict a poor OS (HR = 1.58, 95% CI = 1.38-1.81, P <.000) and DFS/PFS (HR = 1.72, 95% CI = 1.26-2.33, P = .001). Subgroup analyses showed that PD-L1 overexpression was significantly related to the poor OS in patients with breast (HR = 1.98, 95% CI = 1.15-3.41, P = .014), urothelial (HR = 2.24, 95% CI = 1.61-3.12, P <.000), renal (HR = 3.30, 95% CI = 2.23-4.86, P <.000), and gastric cancers (HR = 1.56, 95% CI = 1.02-2.37, P = .040). Furthermore, PD-L1 overexpresion was significantly associated with poor DFS/PFS in patients with hepatocellular carcinoma (HCC) (HR = 1.72, 95% CI = 1.21-2.46, P = .003), melanoma (HR = 3.39, 95% CI = 2.02-5.69, P <.000), and renal carcinoma, (HR = 5.04, 95% CI = 2.87-8.86, P <.000). The adverse prognostic impact of PD-L1 was observed in patients of different ethnicities.ConclusionsThe findings of this meta-analysis suggest the correlation of PD-L1 overexpression with worse OS in patients with solid tumors. However, the correlations differed according to tumor types.
| S-EPMC5419898 | biostudies-literature