Department of Orthopedics, The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital) , Suzhou City, 215000, Jiangsu Province, China.
Cell Mol Biol (Noisy-le-grand). 2024 Mar 31;70(3):110-115. doi: 10.14715/cmb/2024.70.3.16.
DNA damage response (DDR) plays a vital role in the development of cancer. Nevertheless, in osteosarcoma, the potential of DDR-related genes (DDRGs) remains unclear. Thus, the current research is intended to investigate the mechanisms of DDRGs in the development of osteosarcoma and to explore potential DDR-related biomarkers in forecasting the prognosis of osteosarcoma patients. The osteosarcoma genomic data from TCGA, GEO and cBioPortal databases were utilized for screening and identification of differentially expressed DDRGs (DEDDRGs). Consensus clustering analysis was performed to identify different subtypes of osteosarcoma based on the expressions of DDRGs. Key DEDRRGs were identified by overlapping DEDRRGs between different subtypes and DEDRRGs between tumor and control samples. Univariate, as well as LASSO regressions, were further applied to obtain robust prognostic signatures. GSVA and ssGSEA analysis were implemented to explore the underlying mechanisms of prognostic DDRG signature in regulating osteosarcoma. In addition, the drug sensitivity of patients in low- and high-risk groups was evaluated using pRRophetic algorithm. A total of 43 key DEDRRGs were identified. Followed by univariate Cox along with LASSO regression analyses, CDK6, CSF1R, EGFR, ERBB4, GATA3 and SOCS1 were identified as prognostic signatures in osteosarcoma. Cox regressions revealed that the risk score was an independent prognostic factor in osteosarcoma. DDR may affect osteosarcoma via regulating immune microenvironment along with influencing cell proliferation, migration, adhesion and apoptosis. The chemotherapeutic response between patients in low- and high-risk groups was much different. The role of DDRGs in osteosarcoma and identified six DDR-linked biomarkers for forecasting the prognosis of osteosarcoma patients. Our outcomes enhanced the understanding of DDR-related molecular mechanisms involved in osteosarcoma and provided potential therapeutic targets for osteosarcoma patients.
DNA 损伤反应 (DDR) 在癌症的发展中起着至关重要的作用。然而，在骨肉瘤中，DDR 相关基因 (DDRGs) 的潜力尚不清楚。因此，本研究旨在探讨 DDRGs 在骨肉瘤发生发展中的机制，并探索潜在的 DDR 相关生物标志物，以预测骨肉瘤患者的预后。从 TCGA、GEO 和 cBioPortal 数据库中获取骨肉瘤基因组数据，用于筛选和鉴定差异表达的 DDRGs（DEDDRGs）。基于 DDRGs 的表达，通过共识聚类分析来识别不同的骨肉瘤亚型。通过不同亚型之间的 DEDRRGs 重叠和肿瘤与对照样本之间的 DEDRRGs 重叠来识别关键的 DEDRRGs。通过单变量和 LASSO 回归进一步获得稳健的预后特征。进行 GSVA 和 ssGSEA 分析，以探讨预后 DDRG 特征调节骨肉瘤的潜在机制。此外，还使用 pRRophetic 算法评估低风险和高风险组患者的药物敏感性。共鉴定出 43 个关键的 DEDRRGs。通过单变量 Cox 以及 LASSO 回归分析，鉴定出 CDK6、CSF1R、EGFR、ERBB4、GATA3 和 SOCS1 是骨肉瘤的预后标志物。Cox 回归显示，风险评分是骨肉瘤的一个独立预后因素。DDR 可能通过调节免疫微环境以及影响细胞增殖、迁移、黏附和凋亡来影响骨肉瘤。低风险和高风险组患者的化疗反应存在很大差异。DDRGs 在骨肉瘤中的作用及鉴定出 6 个用于预测骨肉瘤患者预后的 DDR 相关生物标志物。本研究结果增强了对骨肉瘤中涉及的 DDR 相关分子机制的理解，并为骨肉瘤患者提供了潜在的治疗靶点。
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