Xie Zhihui, Yang Tiantian, Zhou Chuchu, Xue Zixin, Wang Jianjun, Lu Feng
Department of Medical Oncology, Huaihe Hospital of Henan University, Kaifeng, China.
Department of Immunology, School of Basic Medical Sciences, Henan University, Kaifeng, China.
Mol Carcinog. 2025 Mar;64(3):383-398. doi: 10.1002/mc.23854. Epub 2024 Nov 27.
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.
NLRP12在细胞功能行为和免疫稳态中发挥着重要作用，影响炎症、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）的具体影响及其对卵巢癌（OV）异质性的作用。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OV预后和免疫浸润的关系。进行体外实验以评估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，高表达与不良预后相关。此外，NLRP12表达与OV中各种免疫细胞的浸润以及免疫检查点分子的表达呈正相关。对癌症免疫图谱（TCIA）数据库的分析显示，NLRP12表达较低的OV患者可能对免疫治疗，特别是CTLA4阻断剂表现出更强的反应，这一发现已在动物实验中得到验证。此外，该研究强调了NLRP12通过促进卵巢癌细胞的上皮-间质转化（EMT）来影响OV患者预后的作用。最后，我们鉴定出一种潜在的治疗化合物五味子乙素（Schi B），它通过与与NLRP12相关的转录因子SPI1结合来降低卵巢癌细胞中NLRP12的表达。我们的研究结果表明，NLRP12是预测OV不良结局的关键免疫相关生物标志物，靶向NLRP12可能代表未来OV患者一种有前景的治疗方法。
