ANALYSIS OF THE ROLE OF THE PDCD1 GENE IN THE SEVERITY AND OUTCOME OF LYMPHOPROLIFERATIVE NEOPLASMS

Abstract

Objective: The aim of this study was to evaluate the expression of the PDCD1 gene in patients with lymphoma and multiple myeloma regarding disease severity and outcome. Several studies suggest that this gene is overexpressed in multiple types of cancer, but few directly associate it with lymphoproliferative neoplasms. Materials and Methods: This is a primary, observational cohort study that collected peripheral blood samples from patients with lymphoma or multiple myeloma treated at the Clinical Hospital of Uberaba/MG. RNA was extracted and transcribed into cDNA, and gene expression quantification was performed using the RT-qPCR method. Sociodemographic and clinical data were obtained from electronic medical records. Healthy individuals without a history of neoplasms were also included in the study. Results: It was analyzed 27 controls and 49 patients which were 32 (65.30%) having lymphoma, 17 (34.69%) with multiple myeloma. The median age of the controls was 55 years (ranging from 28 to 75 years), and of the patients was 61 years (ranging from 22 to 92 years). Among the controls, 51.85% were female, and in the patients, this percentage was 61.22%. It was observed that healthy individuals expressed more PDCD1 compared to patients with multiple myeloma (p = 0.0290), which was not observed concerning lymphoma. There was also no difference in gene expression between patients with lymphoma and multiple myeloma. Regarding severity, patients with stage IV lymphomas showed higher PDCD1 expression compared to other stages of the disease (p = 0.0457). Concerning the outcome, the median expression of the PDCD1 gene was approximately a hundredfold higher in patients with lymphoma and a thousandfold higher in patients with myeloma who deceased when compared to individuals who remained alive, though not statistically significant. Discussion: The PDCD1 gene is responsible for maintaining immune tolerance, preventing the development of autoimmune diseases, and controlling hyperinflammation. Concerning neoplasms, the PDCD1 gene's action can promote evasion of the host immune response through the binding of PD-1 to its ligand (PD-L1), leading to anergic T lymphocytes. This mechanism occurs when PD-L1 on cancer cells binds to T cell PD-1, causing phosphorylation in Immunoreceptor Tyrosine-based Activation Motif and Immunoreceptor Tyrosine-based Inhibition Motif, inhibiting T-cell receptor and suppressing T cell function, making it difficult to eliminate target cells. This finding justifies the higher PDCD1 quantification in stage IV lymphoma. The difference in gene expression concerning the outcome was not statistically significant, but it may be due to the sample size, limiting this analysis. Conclusion: The expression of the PDCD1 gene was higher in healthy individuals compared to patients with lymphoproliferative neoplasms. Additionally, it appears that as lymphoma becomes more severe PDCD1 gene expression increases. Concerning the outcome, although the analyses were not statistically significant, it was observed that a worse outcome might be associated with higher gene expression. Therefore, the importance of the PDCD1 gene is notable, especially considering the use of pathway blockers in many types of neoplasms.