NLRP12的综合生物信息学分析和实验研究揭示其在卵巢癌中的预后价值和潜在功能

IF 3 2区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Molecular Carcinogenesis Pub Date : 2025-03-01 Epub Date: 2024-11-27 DOI:10.1002/mc.23854
Zhihui Xie, Tiantian Yang, Chuchu Zhou, Zixin Xue, Jianjun Wang, Feng Lu
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引用次数: 0

摘要

NLRP12在细胞功能行为和免疫稳态中发挥着重要作用,影响着炎症、肿瘤发生和预后。本研究旨在通过生物信息学分析和实验验证,探讨其对肿瘤微环境(TME)的特殊作用及其对卵巢癌(OV)异质性的贡献。利用各种生物信息学数据库和临床标本,我们研究了NLRP12的表达及其与卵巢癌预后和免疫浸润的关系。我们还进行了体外试验,以评估 NLRP12 对 OV 细胞增殖和侵袭的影响。我们的研究结果表明,NLRP12在OV中上调,高表达与预后不良相关。此外,NLRP12的表达与OV中各种免疫细胞的浸润和免疫检查点分子的表达呈正相关。对癌症免疫组图谱(TCIA)数据库的分析表明,NLRP12表达较低的OV患者对免疫疗法,尤其是CTLA4阻断剂的反应可能会增强,这一发现在动物实验中得到了验证。此外,研究还强调了 NLRP12 通过促进卵巢癌细胞的上皮-间质转化(EMT)而影响卵巢癌患者预后的作用。最后,我们发现了一种潜在的治疗化合物--Schisandrin B(Schi B),它能通过与 NLRP12 相关的转录因子 SPI1 结合,降低卵巢癌细胞中 NLRP12 的表达。我们的研究结果表明,NLRP12是预测卵巢癌不良预后的重要免疫相关生物标志物,靶向NLRP12可能是未来治疗卵巢癌患者的一种有前途的方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Integrative Bioinformatics Analysis and Experimental Study of NLRP12 Reveal Its Prognostic Value and Potential Functions in Ovarian Cancer.

NLRP12 plays a significant role in cellular functional behavior and immune homeostasis, influencing inflammation, tumorigenesis, and prognosis. This study aimed to explore its specific effects on the tumor microenvironment (TME) and its contribution to heterogeneity in ovarian cancer (OV) through bioinformatics analysis and experimental verification. Utilizing various bioinformatics databases and clinical specimens, we investigated NLRP12 expression and its relationship with OV prognosis and immune infiltration. In vitro assays were conducted to assess the impact of NLRP12 on the proliferation and invasion of OV cells. Our findings indicate that NLRP12 is upregulated in OV, with high expression correlating with a negative prognosis. Furthermore, NLRP12 expression demonstrated a positive correlation with the infiltration of various immune cells and the expression of immune checkpoint molecules in OV. Analysis of The Cancer Immunome Atlas (TCIA) database revealed that OV patients with lower NLRP12 expression may exhibit an enhanced response to immunotherapy, particularly CTLA4 blockers, a finding validated in animal experiments. Additionally, the study emphasized the role of NLRP12 in influencing the prognosis of OV patients by promoting epithelial-mesenchymal transition (EMT) in ovarian cancer cells. Finally, we identified a potential therapeutic compound, Schisandrin B (Schi B), which decreases NLRP12 expression in ovarian cancer cells by binding to the transcription factor SPI1 associated with NLRP12. Our findings suggest that NLRP12 serves as a crucial immune-related biomarker predicting poor outcomes in OV, and targeting NLRP12 may represent a promising therapeutic approach for OV patients in the future.

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来源期刊
Molecular Carcinogenesis
Molecular Carcinogenesis 医学-生化与分子生物学
CiteScore
7.30
自引率
2.20%
发文量
112
审稿时长
2 months
期刊介绍: Molecular Carcinogenesis publishes articles describing discoveries in basic and clinical science of the mechanisms involved in chemical-, environmental-, physical (e.g., radiation, trauma)-, infection and inflammation-associated cancer development, basic mechanisms of cancer prevention and therapy, the function of oncogenes and tumors suppressors, and the role of biomarkers for cancer risk prediction, molecular diagnosis and prognosis.
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