Zhao Wenrui, Wang Yameng, Zhu Junchao, Arya Shahrzad, Huang Guowen, Li Shengqin, Chen Qi, Liu Xijuan, Yuan Jinghong, Jia Jingyu
Department of Orthopaedics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China.
Institute of Orthopaedics of Jiangxi Province, Nanchang, Jiangxi, China.
Sci Rep. 2025 Mar 17;15(1):9180. doi: 10.1038/s41598-025-93167-2.
Osteosarcoma, the most common primary bone cancer in children and adolescents, presents significant challenges, particularly in metastasis and recurrence, resulting in poor survival rates. This study explores the role of PANoptosis-a complex cell death mechanism involving pyroptosis, apoptosis, and necroptosis-in osteosarcoma by identifying relevant long non-coding RNAs (lncRNAs) and their prognostic significance. Bioinformatics analyses used RNA expression data from the GEO and TARGET databases to identify differentially expressed genes (DEGs) and PANoptosis-related genes (PRGs). Co-expression analysis revealed lncRNAs linked to PRGs, forming a risk prognostic model. Five PRGs and two lncRNAs were significantly associated with prognosis, with the model showing high predictive accuracy (AUC 0.876, 0.787, and 0.794 for 1, 3, and 5 years). Notably, lncRNA AC133552.2 was downregulated in osteosarcoma tissues, correlating with poor survival and reduced immune infiltration. Silencing AC133552.2 promoted cell proliferation and migration, while overexpression inhibited tumor growth and metastasis, confirmed in xenograft models. AC133552.2 emerges as a potential biomarker and therapeutic target, with future research needed to explore its molecular mechanisms and clinical application.
骨肉瘤是儿童和青少年中最常见的原发性骨癌，它带来了重大挑战，尤其是在转移和复发方面，导致生存率低下。本研究通过鉴定相关的长链非编码RNA（lncRNA）及其预后意义，探讨PANoptosis（一种涉及细胞焦亡、凋亡和坏死性凋亡的复杂细胞死亡机制）在骨肉瘤中的作用。生物信息学分析利用来自GEO和TARGET数据库的RNA表达数据来鉴定差异表达基因（DEG）和PANoptosis相关基因（PRG）。共表达分析揭示了与PRG相关的lncRNA，构建了一个风险预后模型。五个PRG和两个lncRNA与预后显著相关，该模型显示出较高的预测准确性（1年、3年和5年的AUC分别为0.876、0.787和0.794）。值得注意的是，lncRNA AC133552.2在骨肉瘤组织中表达下调，与较差的生存率和免疫浸润减少相关。在异种移植模型中证实，沉默AC133552.2可促进细胞增殖和迁移，而过表达则抑制肿瘤生长和转移。AC133552.2成为一种潜在的生物标志物和治疗靶点，未来需要进一步研究以探索其分子机制和临床应用。
