NANP作为与唾液酸化相关的预后预测因子在弥漫性大B细胞淋巴瘤中发挥调控作用

NANP as a Prognostic Predictor Associated with Sialylation Plays a Regulatory Role in Diffuse Large B-Cell Lymphoma

摘要: 背景：唾液酸化是由特定唾液酸转移酶催化的酶促过程，已有研究显示其与多种恶性肿瘤的发病机制相关。然而，唾液酸化在弥漫性大B细胞淋巴瘤(DLBCL)中的作用尚未明确。本研究旨在探讨DLBCL中与唾液酸化相关的特征。方法：我们首先分析了DLBCL与正常样本中唾液酸化相关基因(SRGs)的表达谱。随后，通过Cox回归和LASSO回归分析筛选出与预后相关的基因，并构建了一个风险模型。接着，我们在DLBCL细胞系中验证了这些预后基因的表达，并通过敲低NANP基因，探讨其对细胞周期和凋亡的影响。此外，我们还分析了高风险组与低风险组在免疫细胞浸润和化疗敏感性方面的差异。结果：与正常组织相比，DLBCL中大多数SRGs的表达呈现异常。我们鉴定并利用七个SRGs构建了一个准确的预后风险模型。值得注意的是，与高风险组相比，低风险组患者的死亡率较低，生存期较长。随后，我们采用qRT-PCR验证了结果，发现NANP显著上调。进一步的Western blot分析和流式细胞术实验证实，敲低NANP可诱导DLBCL细胞凋亡，并导致细胞周期阻滞于G0/G1期。结论：本研究揭示了DLBCL中SRGs的异常表达及其与临床特征的相关性。所构建的风险模型有望为DLBCL的精准预后分层及免疫治疗评估提供理论基础。

Abstract: Background: Sialylation, the enzymatic process catalyzed by specific sialyltransferases, has been implicated in the pathogenesis of various malignancies. However, the role of sialylation in Diffuse Large B-Cell Lymphoma (DLBCL) remains undefined. Herein, we aimed to investigate the sialylation-related signature in DLBCL. Methods: We initially analyzed the expression profiles of Sialylation-Related Genes (SRGs) in DLBCL and normal samples. Subsequently, we identified prognostic genes and developed a risk model using Cox and LASSO regression analyses. Next, we validated the expression of prognostic genes in DLBCL cell lines. We then knocked down the NANP gene in DLBCL cells to explore its impact on the cell cycle and apoptosis. Furthermore, we examined the differences in immune cell infiltration and chemotherapy sensitivity between high-risk and low-risk groups. Results: In contrast to normal tissues, the majority of SRGs exhibited dysregulated expression in DLBCL. We have identified and utilized seven SRGs to develop an accurate prognostic risk model. Notably, individuals classified in the low-risk group exhibited reduced mortality and prolonged survival in comparison to the high-risk group. Following this, we employed qRT-PCR to validate our findings, uncovering a marked upregulation of NANP. Subsequent Western blot analysis and flow cytometry assays confirmed that the knockdown of NANP led to the induction of apoptosis and cell cycle arrest at the G0/G1 phase in DLBCL. Conclusions: Our study elucidates the dysregulated expression of SRGs in DLBCL and their correlation with clinical features. The risk model we developed is anticipated to establish a theoretical foundation for precise prognostic stratification and immunotherapeutic assessment in DLBCL.