Abstract:Programmed cell death-ligand 1(PD-L1) was expressed in various malignancies, and interaction with its receptor programmed cell death 1 (PD-1) often contributed to immune evasion of tumor cells. In this study, we explored the expression of PD-L1 and its correlation with clinical outcomes in gliomas.Clinicopathological data of 229 patients with gliomas was collected. PD-L1 expression was assessed by tissue-microarray-based immunohistochemistry. Over 5% of tumor cells with cytoplasm or membrane staining was defin… Show more
“…c Kaplan-Meier survival curve for patients with high-grade gliomas (n = 100).Overall survival rate in patients with high expression of WTAP in glioma was significantly lower than in patients with low expression of WTAP. (log rank test P < 0.001) Zeng et al 2016). In our study, besides age and WHO grade, WTAP expression was showed closely associated with overall survival and to be an independent prognostic factor.…”
Wilms' tumor 1-associating protein (WTAP) interacts with the Wilms' tumor 1 gene. Although originally classified as a tumor suppressor, WTAP was later found to be over-expressed in glioblastoma which is regarded as a grade IV astrocytoma. However, the expression in other glioma grades and the relationship between WTAP expression and the prognosis of glioma patients are still unknown. In this study, we investigated WTAP expression in 169 different types of glioma cases using western blot analysis and immunohistochemistry assay. Further, we evaluated the association of WTAP expression with clinicopathological characteristics using chi-square test and Spearman's correlation test. We used univariate and multivariate Cox regression analyses to evaluate the independency of diferent WTAP expression. Then, the survival curves were calculated using the Kaplan-Meier method. Results showed that WTAP was over-expressed in glioma tissues, and the expression was closely correlated with glioma grade. Moreover, high WTAP expression was correlated with poor postoperative survival in glioma patients. WTAP may serve as a novel prognostic marker.
“…c Kaplan-Meier survival curve for patients with high-grade gliomas (n = 100).Overall survival rate in patients with high expression of WTAP in glioma was significantly lower than in patients with low expression of WTAP. (log rank test P < 0.001) Zeng et al 2016). In our study, besides age and WHO grade, WTAP expression was showed closely associated with overall survival and to be an independent prognostic factor.…”
Wilms' tumor 1-associating protein (WTAP) interacts with the Wilms' tumor 1 gene. Although originally classified as a tumor suppressor, WTAP was later found to be over-expressed in glioblastoma which is regarded as a grade IV astrocytoma. However, the expression in other glioma grades and the relationship between WTAP expression and the prognosis of glioma patients are still unknown. In this study, we investigated WTAP expression in 169 different types of glioma cases using western blot analysis and immunohistochemistry assay. Further, we evaluated the association of WTAP expression with clinicopathological characteristics using chi-square test and Spearman's correlation test. We used univariate and multivariate Cox regression analyses to evaluate the independency of diferent WTAP expression. Then, the survival curves were calculated using the Kaplan-Meier method. Results showed that WTAP was over-expressed in glioma tissues, and the expression was closely correlated with glioma grade. Moreover, high WTAP expression was correlated with poor postoperative survival in glioma patients. WTAP may serve as a novel prognostic marker.
“…In a study of 229 glioma (grades I–IV) patients, Zeng et al [17] found no significant associations between PD-L1 expression and OS. Using the median survival time (12 months) as a cut-off point, these authors found that a high level of PD-L1 expression was significantly associated with the poor OS of patients who survived and were followed up over 12 months.…”
Section: Pd-l1 Expression and Prognosis Value In Gliomasmentioning
Gliomas are the most common type of primary brain tumor in adults. High-grade neoplasms are associated with poor prognoses, whereas low-grade neoplasms are associated with 5-year overall survival rates of approximately 85%. Despite considerable progress in treatment modalities, the outcomes remain dismal. As is the case with many other tumors, gliomas express or secrete several immunosuppressive molecules that regulate immune cell function. Programmed death-ligand 1 (PD-L1) is a coinhibitory ligand that is predominantly expressed by tumor cells. The binding of PD-L1 to its receptor PD-1 has been demonstrated to induce an immune escape mechanism and to play a critical role in tumor initiation and development. Encouraging results following the blockade of the PD-1/PD-L1 pathway have validated PD-L1 or PD-1 as a target for cancer immunotherapy. Studies have reported that the PD-1/PD-L1 pathway plays a key role in glioma progression and in the efficacy of immunotherapies. Thus, progress in research into PD-L1 will enable us to develop a more effective and individualized immunotherapeutic strategy for gliomas. In this paper, we review PD-L1 expression, PD-L1-mediated immunosuppressive mechanisms, and the clinical applications of PD-1/PD-L1 inhibitors in gliomas. Potential treatment strategies and the challenges that may occur during the clinical development of these agents for gliomas are also reviewed.
“…Ultimately, 4 articles were included in this meta-analysis (Fig. 1) 9–12 .Figure 1Flow diagram of the literature search and study selection protocols.
…”
Section: Resultsmentioning
confidence: 99%
“…9
DenmarkProteinGlioblastomaNMIFCNANon-percentage ¶
176/1135.29UA4.67 (1.42–15.43)6Berghoff, A. S. 11
†
AustriaProteinGlioblastomaFFPEIHCMembranousPercentage (≥5%)11744/7337.61UA1.22 (0.83–1.8)7GeneGlioblastomaTCGAAgilent microarray—Median PD-L1 expression levels446223/22350MA1.036 (0.87–1.23)Nduom, E. K. 15
†
USAProteinGlioblastomaTMAIHCMembranesPercentage (≥5%)9458/3661.70UA1.74 (1.09–2.77)7GeneGlioblastomaTCGAIllumina RNASeq—0.37149NMNMMA1.52 (1.03–2.25)Zeng, J. 12
ChinaProteinGliomaTMAIHCMembranes/CytoplasmPercentage (≥5%)229117/11251.09UA1.05 (0.76–1.47)8Note: † This research contains two cohorts, one is protein cohort, and the other is gene cohort.
§ Cut off criterion for PD-L1 Positive.
¶ >10 cells/field tumor cells.
# HR for OS and positive PD-L1 expression.Abbreviations: IHC, Immunohistochemistry; IFC, Immunofluorescence histochemistry; FFPE, Formalin-fixed paraffin-embedded; TMA, tissue microarray; TCGA, The Cancer Genome Atlas.UA, univariate analysis; MA, multivariate analysis; HR, Hazard ratio; CI, Confidence interval; NM, Not mentioned; NOS, Newcastle-Ottawa scores.
…”
Section: Resultsmentioning
confidence: 99%
“…10
3227Zeng, J. et al . 12
3238
† Selection (0~4 points).(1) Representativeness of the exposed cohort (1 point, truly or somewhat representative of the average level in the community; 0 point, selected group of users or no description of the derivation of the cohort).(2) Selection of the non-exposed cohort (1 point, drawn from the same community as the exposed cohort; 0 point, drawn from a different source or no description of the derivation of the non-exposed cohort).(3) Ascertainment of exposure (1 point, secure record or structured interview; 0 point, written self-report or no description).(4) Demonstration that outcome of interest was not present at start of study (1 point, yes; 0 point, no).
‡ Comparability (0~2 points) (2 points, study controls for the most important factor and any additional factor; 1 point, study controls for the most important factor or any additional factor; 0 point, study controls without the most important factor or any additional factor).
§ Outcome (0~3 points).(1) Assessment of outcome (1 point, independent blind assessment or record linkage; 0 point, self-report or no description).(2) Was follow-up long enough for outcomes to occur (1 point, yes; 0 point, no).(3) Adequacy of follow up of cohorts (1 point, complete follow up or subjects lost to follow up unlikely to introduce bias; 0 point, follow up rate <80% and no description of those lost, or no statement).
¶ The quality score was ranked as low (≤5points) or high (≥6 points).
…”
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.
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