关键词: 弥漫大B细胞淋巴瘤, NF-κB/p65, 程序性死亡［蛋白］-1, 程序性死亡［蛋白］配体-1, 相关性

Abstract: Background and purpose: Activation of NF-κB pathway is an important mechanism in the pathogenesis of diffuse large B-cell lymphoma (DLBCL), which is also associated with the activation of programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) pathway, and protein expressions of NF-κB/p65, PD-1 and PD-L1 are associated with poor prognosis in patients, but the relationship between them has not been investigated. This study attempted to investigate the correlation between high p65 protein expression and protein and mRNA levels of PD-1 and PD-L1, and to analyze the correlation among p65, PD-1 and PD-L1 protein expressions and the clinicopathological characteristics and overall survival (OS). Methods: A total of 90 cases of DLBCL tissue wax blocks from Department of Pathology in Guizhou Medical University were enrolled in this study from Jan. 2010 to Dec. 2017. The p65 protein was detected by immunohistochemical staining, and DLBCL tissues were divided into high expression group and low expression group. PD-1 protein in each group was detected by immunohistochemical staining, while the expression of PD-L1 in tumor cells and tumor microenvironment cells (mPD-L1) ［tumor-infiltrating lymphocyte (TIL)］ was detected by immunohistochemical double labeling staining. The relative mRNA expressions of PD-1 and PD-L1 in the p65 high expression group and p65 low expression group were detected by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR). The clinicopathological data were collected, and the follow-up was done. Finally, the experimental data were statistically analyzed. Results: Among all the samples, p65 positive rate was 61.11% (55/90), PD-1 positive rate was 32.22% (29/90), PD-L1 positive rate in tumor cells was 24.44% (22/90), and PD-L1 positive rate in tumor microenvironment cells (mPD-L1) was 28.89% (26/90). p65 high expression was not correlated with PD-1 protein or mRNA (P>0.05), whereas p65 high expression was correlated with PD- L1 protein expression in tumor cells or microenvironment cells (P=0.022, P=0.015). There was a statistically significant difference in PD-L1 mRNA expression between groups, and the p65+ group was relatively higher (P=0.012). Clinical data showed that PD-1 positive rate was associated with high IPI score (P=0.044), and PD-L1 positive rate was associated with high IPI score and the occurrence of symptoms B (P=0.007, P=0.001). Kaplan-Meier analysis suggested that the expressions of p65, PD-1, PD-L1 and mPD-L1 were correlated with the OS of the patients with DLBCL, and the OS of patients who had p65 high expression, positive PD-1, PD-L1 and mPD-L1 was relatively short (P=0.038, 0.015, 0.028, 0.010). Conclusion: The up-regulated expressions of PD-L1 protein and mRNA are correlated with the high expression of p65 protein in DLBCL. Protein expressions of p65, PD-1, PD-L1 and mPD-L1 are related to shorter OS in patients, and these protein expressions have potential value for clinical and prognostic evaluation of survival.

Key words: Diffuse large B-cell lymphoma, NF-κB/p65, Programmed death-1, Programmed death ligand-1, Correlation