Minimally Invasive Spinal Surgery Center, Luoyang Orthopedic-Traumatological Hospital of Henan Province (Henan Provincial Orthopedic Hospital), Zhengzhou 450018, China.
Department of Orthopedics, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou 450003, China.
Aging (Albany NY). 2024 Jan 12;16(1):665-684. doi: 10.18632/aging.205411.
Anoikis is essential for the progression of many malignant tumors. However, the understanding of anoikis' roles in osteosarcoma remains scarce. This study conducted an extensive bioinformatics analysis to identify anoikis-related genes (ARGs), developed ARGs modeles for predicting OS and RFS, and evaluated the effect of these ARGs on osteosarcoma cell migration and invasion. The GSE16088 and GSE28425 datasets provided the differentially expressed genes (DEGs). The prognostic significance and functions of these DEGs were systematically investigated using several bioinformatics techniques. Transwell assays were conducted to determine the effect of OGT on osteosarcoma cell migration and invasion. Seven genes were identified as hub genes, including , and , while 71 ARGs were identified as DEGs. Four ARGs-, and -were used to develop an RFS-predicting model, whereas seven ARGs-, and -were used to develop an OS-predicting model in patients with osteosarcoma. In both the training and validation cohorts, high-risk group patients had significantly shorter OS and RFS duration than low-risk group patients. Furthermore, using the aforementioned ARGs, we developed clinically applicable nomograms for OS and RFS prediction. The proportion of tumor-infiltrating immune cells was significantly linked to risk scores. experiments revealed that knocking down OGT significantly inhibited the ability of MG63 and U2OS cells to invade and migrate. ARG-based gene signatures reliably predicted RFS and OS in osteosarcoma, and OGT showed promise as a potential biomarker. These findings contribute to a better understanding of ARGs' prognostic roles in osteosarcoma.
失巢凋亡对于许多恶性肿瘤的进展是必不可少的。然而,人们对其在骨肉瘤中的作用的理解仍然很少。本研究进行了广泛的生物信息学分析,以鉴定与失巢凋亡相关的基因(ARGs),建立用于预测 OS 和 RFS 的 ARGs 模型,并评估这些 ARGs 对骨肉瘤细胞迁移和侵袭的影响。GSE16088 和 GSE28425 数据集提供了差异表达基因(DEGs)。使用几种生物信息学技术系统地研究了这些 DEGs 的预后意义和功能。通过 Transwell 测定法确定 OGT 对骨肉瘤细胞迁移和侵袭的影响。鉴定出 7 个基因作为 hub 基因,包括、和、而 71 个 ARGs 被鉴定为 DEGs。使用 4 个 ARGs-、和-构建 RFS 预测模型,而使用 7 个 ARGs-、和-构建 OS 预测模型用于骨肉瘤患者。在训练和验证队列中,高风险组患者的 OS 和 RFS 持续时间明显短于低风险组患者。此外,使用上述 ARGs,我们开发了用于 OS 和 RFS 预测的临床适用的列线图。肿瘤浸润免疫细胞的比例与风险评分显著相关。实验表明,敲低 OGT 显著抑制了 MG63 和 U2OS 细胞的侵袭和迁移能力。基于 ARG 的基因特征可靠地预测了骨肉瘤的 RFS 和 OS,而 OGT 有望成为一种潜在的生物标志物。这些发现有助于更好地理解 ARGs 在骨肉瘤中的预后作用。