Liu Wei, Xu Ze, Li Mingdong, Zhu Nan, Zhang Shuo, Zhang Qilun, Zhan Junfeng
Department of Orthopedics, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, P.R. China.
Institute of Orthopedics, Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, P.R. China.
Oncol Lett. 2025 Jun 10;30(2):387. doi: 10.3892/ol.2025.15134. eCollection 2025 Aug.
Understanding the metabolic processes in osteosarcoma (OS) is key for the development of effective diagnostic and therapeutic modalities. Propionate metabolism has been found to have a crucial role in certain cancers, highlighting its potential relevance in OS. The aim of the present study was to identify novel prognostic indicators for OS based on gene expression profiles and clinical data. Differentially expressed genes (DEGs) in OS and propionate metabolism-associated genes were identified by the analysis of public datasets. Subsequently, functional enrichment analysis was performed and a protein-protein interaction network was constructed. Least absolute shrinkage and selection operato-Cox regression analysis was then conducted to construct a risk model, which was used to establish high- and low-risk patient groups, and the association of the risk model with immune cell infiltration and immunotherapy was assessed. Furthermore, a prognostic nomogram was constructed. In addition, cell assays were conducted to evaluate the influence of prognostic gene knockdown on OS cells. The bioinformatics analysis led to the identification of 18 DEGs associated with propionate metabolism in OS, and the risk score model revealed two prognostic genes, namely 4-aminobutyrate aminotransferase (ABAT) and aldehyde dehydrogenase 7 family member A1 (ALDH7A1). Immune infiltration analysis highlighted a significant difference between high- and low-risk groups, indicating a potential impact on the response to immune therapy. In addition, the propionate metabolism-related gene signatures effectively distinguished OS patients with distinct clinical outcomes and tumor microenvironments, and single-cell analysis revealed associations of ABAT and ALDH7A1 with immune cell infiltration. Furthermore, cell assays revealed that the knockdown of ABAT promoted OS cell growth, migration and invasion. In conclusion, the present study emphasized the relevance of propionate metabolism in OS and introduced a novel gene signature for clinical outcome prediction. Furthermore, the identified genes, ABAT and ALDH7A1, may hold promise as potential therapeutic targets.
了解骨肉瘤（OS）中的代谢过程是开发有效诊断和治疗方法的关键。已发现丙酸盐代谢在某些癌症中起关键作用，凸显了其在骨肉瘤中的潜在相关性。本研究的目的是基于基因表达谱和临床数据确定骨肉瘤的新预后指标。通过对公共数据集的分析，确定了骨肉瘤中的差异表达基因（DEG）和丙酸盐代谢相关基因。随后进行功能富集分析并构建蛋白质-蛋白质相互作用网络。然后进行最小绝对收缩和选择算子-Cox回归分析以构建风险模型，该模型用于建立高风险和低风险患者组，并评估风险模型与免疫细胞浸润和免疫治疗的关联。此外，构建了预后列线图。此外，进行细胞实验以评估预后基因敲低对骨肉瘤细胞的影响。生物信息学分析导致在骨肉瘤中鉴定出18个与丙酸盐代谢相关的DEG，风险评分模型揭示了两个预后基因，即4-氨基丁酸转氨酶（ABAT）和醛脱氢酶7家族成员A1（ALDH7A1）。免疫浸润分析突出了高风险和低风险组之间的显著差异，表明对免疫治疗反应有潜在影响。此外，丙酸盐代谢相关基因特征有效地区分了具有不同临床结果和肿瘤微环境的骨肉瘤患者，单细胞分析揭示了ABAT和ALDH7A1与免疫细胞浸润的关联。此外，细胞实验表明ABAT敲低促进了骨肉瘤细胞的生长、迁移和侵袭。总之，本研究强调了丙酸盐代谢在骨肉瘤中的相关性，并引入了一种用于临床结果预测的新基因特征。此外，鉴定出的基因ABAT和ALDH7A1可能有望成为潜在的治疗靶点。
