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建立了一个基于 NSUN3 的预后模型,用于评估肝癌的预后和对免疫治疗的反应。

A Prognostic Model Based on NSUN3 Was Established to Evaluate the Prognosis and Response to Immunotherapy in Liver Hepatocellular Carcinoma.

机构信息

Dongguan Institute of Clinical Cancer Research, The Tenth Affiliated Hospital of Southern Medical University, China.

Dongguan Key Laboratory of Precision Diagnosis and Treatment for Tumors, The Tenth Affiliated Hospital of Southern Medical University, China.

出版信息

Mediators Inflamm. 2023 Apr 18;2023:6645476. doi: 10.1155/2023/6645476. eCollection 2023.

Abstract

It is difficult for traditional therapies to further improve the prognosis of hepatocellular carcinoma (LIHC), and immunotherapy is considered to be a promising approach to overcome this dilemma. However, only a minority of patients benefit from immunotherapy, which greatly limits its application. Therefore, it is particularly urgent to elucidate the specific regulatory mechanism of tumor immunity so as to provide a new direction for immunotherapy. NOP2/Sun RNA methyltransferase 3 (NSUN3) is a protein with RNA binding and methyltransferase activity, which has been shown to be involved in the occurrence and development of a variety of tumors. At present, the relationship between NSUN3 and immune implication in LIHC has not been reported. In this study, we first revealed that NSUN3 expression is upregulated in LIHC and that patients with high NSUN3 expression have a poor prognosis through multiple databases. Pathway enrichment analysis demonstrated that NSUN3 may be participated in cell adhesion and cell matrix remodeling. Next, we obtained a set of genes coexpressed with NSUN3 (NCGs). Further LASSO regression was performed based on NCGs, and a risk score model was constructed, which proved to have good predictive power. In addition, Cox regression analysis revealed that the risk score of NCGs model was an independent risk factor for LIHC patients. Moreover, we established a nomogram based on the NCGs-related model, which was verified to have a good predictive ability for the prognosis of LIHC. Furthermore, we investigated the relationship between NCGs-related model and immune implication. The results implied that our model was closely related to immune score, immune cell infiltration, immunotherapy response, and multiple immune checkpoints. Finally, the pathway enrichment analysis of NCGs-related model showed that the model may be involved in the regulation of various immune pathways. In conclusion, our study revealed a novel role of NSUN3 in LIHC. The NSUN3-based prognostic model may be a promising biomarker for inspecting the prognosis and immunotherapy response of LIHC.

摘要

传统疗法难以进一步改善肝细胞癌(LIHC)的预后,免疫疗法被认为是克服这一困境的有前途的方法。然而,只有少数患者受益于免疫疗法,这极大地限制了其应用。因此,阐明肿瘤免疫的具体调节机制尤为迫切,以期为免疫疗法提供新的方向。NOP2/Sun RNA 甲基转移酶 3(NSUN3)是一种具有 RNA 结合和甲基转移酶活性的蛋白质,已被证明参与多种肿瘤的发生和发展。目前,NSUN3 与 LIHC 中的免疫含义之间的关系尚未报道。在本研究中,我们首先通过多个数据库揭示 NSUN3 在 LIHC 中表达上调,并且高 NSUN3 表达的患者预后不良。通路富集分析表明,NSUN3 可能参与细胞黏附和细胞基质重塑。接下来,我们获得了一组与 NSUN3 共表达的基因(NCGs)。进一步基于 NCGs 进行 LASSO 回归,构建风险评分模型,证明其具有良好的预测能力。此外,Cox 回归分析表明,NCGs 模型的风险评分是 LIHC 患者的独立危险因素。此外,我们基于 NCGs 相关模型建立了一个列线图,验证其对 LIHC 预后具有良好的预测能力。此外,我们研究了 NCGs 相关模型与免疫含义的关系。结果表明,我们的模型与免疫评分、免疫细胞浸润、免疫治疗反应和多个免疫检查点密切相关。最后,NCGs 相关模型的通路富集分析表明,该模型可能参与了各种免疫通路的调节。总之,我们的研究揭示了 NSUN3 在 LIHC 中的新作用。基于 NSUN3 的预后模型可能是评估 LIHC 预后和免疫治疗反应的有前途的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/622b/10129436/76e8e9e7a2b2/MI2023-6645476.001.jpg

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