Integrative Bioinformatics Analysis and Experimental Study of NLRP12 Reveal Its Prognostic Value and Potential Functions in Ovarian Cancer

生物 免疫系统 卵巢癌 癌变 癌症研究 炎症 肿瘤微环境 免疫疗法 生物标志物 癌症 转录因子 免疫学 生物信息学 遗传学 基因
作者
Zhihui Xie,Tiantian Yang,Chuchu Zhou,Zhiyi Xue,Jianjun Wang,Feng Lu
出处
期刊:Molecular Carcinogenesis [Wiley]
卷期号:64 (3): 383-398
标识
DOI:10.1002/mc.23854
摘要

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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