UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia.
Codon Genomics Sdn Bhd, Seri Kembangan Selangor Darul Ehsan, Malaysia.
Iran J Med Sci. 2024 Oct 1;49(10):652-660. doi: 10.30476/IJMS.2023.100149.3234. eCollection 2024 Oct.
Diffuse large B-cell lymphoma (DLBCL) is globally recognized as the most prevalent and aggressive subtype of non-Hodgkin lymphoma. While conventional treatments are effective initially, the disease can become resistant or relapse over time. This study aimed to examine the differentially expressed genes at the transcriptome level and molecular pathways in DLBCL patients.
This investigation utilized RNA sequencing analysis to compare differentially expressed gene samples from five diffuse large B-cell lymphoma patients with two healthy volunteers. These participants were admitted to UKM Medical Center, Kuala Lumpur between 2019 and 2020. The differentially expressed genes were identified using the DESeq2 R package (version 1.10.1) using a negative binomial distribution model. The obtained P values were corrected with the Benjamin and Hochberg method and identified using a False Discovery Rate threshold of <0.05, with log fold change (FC) of ≥2 or ≤-2.
Results showed 73 differentially expressed genes between the two groups, among which 70 genes were downregulated, and three genes were upregulated. The differentially expressed genes analyzed with the Reactome pathway were significantly associated with the downregulation of antimicrobial humoral response (P<0.001), neutrophil degranulation (P<0.001), chemokine receptors bind chemokines (P=0.028), defensins (P=0.028) and metabolism of angiotensinogen (P=0.040).
These findings suggest that the identified pathways may contribute to cancer progression and weaken the immune response in diffuse large B-cell lymphoma patients. This study offers fresh insights into previously undiscovered downstream targets and pathways modulated by diffuse large B-cell lymphoma.
弥漫性大 B 细胞淋巴瘤（DLBCL）是全球公认的最常见和侵袭性最强的非霍奇金淋巴瘤亚型。虽然传统治疗在初期是有效的，但随着时间的推移，疾病可能会产生耐药性或复发。本研究旨在检查 DLBCL 患者在转录组水平和分子途径上的差异表达基因。
本研究利用 RNA 测序分析比较了 2019 年至 2020 年间在马来西亚 UKM 医疗中心就诊的五名弥漫性大 B 细胞淋巴瘤患者和两名健康志愿者的差异表达基因样本。使用 DESeq2 R 包（版本 1.10.1）和负二项分布模型确定差异表达基因。用 Benjamin 和 Hochberg 方法校正获得的 P 值，并使用 False Discovery Rate 阈值 <0.05、对数倍数变化（FC）≥2 或 ≤-2 确定差异表达基因。
结果显示两组之间有 73 个差异表达基因，其中 70 个基因下调，3 个基因上调。通过 Reactome 途径分析的差异表达基因与下调抗菌体液反应（P<0.001）、中性粒细胞脱颗粒（P<0.001）、趋化因子受体结合趋化因子（P=0.028）、防御素（P=0.028）和血管紧张素原代谢（P=0.040）显著相关。
这些发现表明，所确定的途径可能有助于癌症的进展，并削弱弥漫性大 B 细胞淋巴瘤患者的免疫反应。本研究为以前未发现的由弥漫性大 B 细胞淋巴瘤调节的下游靶标和途径提供了新的见解。
