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Relationship of Programmed Death-1 (PD-1) and Programmed Death Ligand-1 (PD-L1) Polymorphisms with Overall Cancer Susceptibility: An Updated Meta-Analysis of 28 Studies with 60 612 Subjects.

ABSTRACT: BACKGROUND Programmed death-1 and its ligand-1 (PD-1/PD-L1) regulate tumor immunotherapy. A large number of studies have explored the relationship between PD-1, PD-L1, and different tumor susceptibility. However, these conclusions are not always consistent. Therefore, we updated this meta-analysis. MATERIAL AND METHODS MEDLINE, Web of Science, EMBASE and other databases were searched systematically to obtain related research. Then, we used STATA15.0 software to carry out the final meta-analysis. The computational advantage is better than OR to evaluate this relationship. RESULTS A total of a total of 28 related studies were involved in our meta-analysis. It was found that PD-1 rs11568821 and rs7421861 increased the overall cancer probability in the allelic genetic model, while PD-1 rs36084323 effectively reduced the risk of cancer in the dominant genetic model. In the homozygous genetic model, PD-L1 rs17718883 effectively increased the probability of tumorigenesis. PD-L1rs4143815 is associated with a reduced incidence of cancer in heterozygote, homozygote and dominant genetic patterns. Subgroup analysis showed that PD-1rs2227981 can promote the susceptibility to breast cancer, while PD-1rs2227982 can reduce the susceptibility to breast cancer. PD-L1 rs2890658 can significantly reduce the risk of lung and liver cancer. CONCLUSIONS PD-1rs11568821, rs36084323, rs7421861, pD-L1rs17718883, and rs4143815 are associated with tumor susceptibility. However, a review based on more experimental evidence is needed to verify our findings.

SUBMITTER: Zhang W

PROVIDER: S-EPMC8162050 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Objectives: Thymic epithelial tumors (TETs) are rare malignant tumors that exhibit heterogeneous histology and clinical behavior. As immune check point inhibitors, drugs targeting anti-programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) have shown remarkable results against many cancers; thus, the importance of PD-1/PD-L1 immunohistochemistry as a predictive or prognostic biomarker has grown. However, limited data on PD-L1 and PD-1 expression in TETs have been reported; moreover, these results have been variable. Here, we examined the expression of PD-1/PD-L1 proteins in TETs and analyzed the clinicopathologic significance of this expression. Patients and Methods: A tissue microarray was constructed using 368 samples of TETs, each in triplicate. Immunohistochemistry for PD-L1 (SP263 assay) and PD-1 in TETs and CD8 in thymic carcinoma (TC) was performed; next, correlations with clinicopathologic characteristics were analyzed. PD-L1high was designated as ?50% of tumor proportion score; PD-1high and CD8high were defined as ?5% and 1% of tumoral immune cells, respectively. Results: The cohort consisted of 308 patients with thymomas and 60 patients with TC. PD-L1 positivity was identified in 90.6% (328/362, ?1%) of TETs, PD-1 expression of intra-/peritumoral T cells was identified in 53.6% (194/362) of TETs and CD8 positivity was identified in 11% (7/60, ?1%) of TC. Of the 362 patients, 141 (39.0%) exhibited high PD-L1 expression (PD-L1high). The PD-L1high thymoma group was correlated with high Masaoka-Koga stage (p < 0.001), type B3 histology (p < 0.001), and myasthenia gravis (p < 0.001). This group exhibited poor overall survival (OS, p = 0.003, log-rank) and worse disease-free survival (DFS, p = 0.042, log-rank). No survival differences were detected between PD-L1high and PD-L1low groups in TC. Additionally, there was no correlation between PD-1 expression and survival in patients with TETs. Multivariate analysis revealed that PD-L1high expression was an independent poor prognostic factor (p = 0.047, HR 2.087, 95% CI, 1.009-4.318) in thymomas. Conclusions: To our knowledge, this is the largest study on TETs published in English literature. This study provides useful information regarding the prognosis of and potential therapeutic options for patients with TETs.

Dataset Information

Relationship of Programmed Death-1 (PD-1) and Programmed Death Ligand-1 (PD-L1) Polymorphisms with Overall Cancer Susceptibility: An Updated Meta-Analysis of 28 Studies with 60 612 Subjects.

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