Zhang Jian, Ding Rui, Wu Tianlong, Jia Jingyu, Cheng Xigao
Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Institute of Orthopedics of Jiangxi Province, Nanchang, China.
Front Cell Dev Biol. 2021 Aug 26;9:705291. doi: 10.3389/fcell.2021.705291. eCollection 2021.
Osteosarcoma is a common malignant tumor that seriously threatens the lives of teenagers and children. Autophagy is an intracellular metabolic process mediated by autophagy-related genes (ARGs), which is known to be associated with the progression and drug resistance of osteosarcoma. In this study, RNA sequence data from TARGET and genotype-tissue expression (GTEx) databases were analyzed. A six autophagy-related long noncoding RNAs (ARLs) signature that accurately predicted the clinical outcomes of osteosarcoma patients was identified, and the relations between immune response and the ARLs prognostic signature were examined. In addition, we obtained 30 ARGs differentially expressed among osteosarcoma tissue and healthy tissue, and performed functional enrichment analysis on them. To screen for prognostic-related ARGs, univariate and LASSO Cox regression analyses were successively applied. Then, multivariate regression analysis was used to complete construction of the prognostic signature of ARGs. Based on the risk coefficient, we calculated the risk score and grouped the patients. Survival analysis showed that high-risk patients evolve with poor prognosis. And we verified the prognosis model in the GSE21257 cohort. Finally, verification was conducted by qRT-PCR and western blot to measure the expression of genes. The results show that autophagy-related marker models may provide a new therapeutic and diagnostic target for osteosarcoma.
骨肉瘤是一种严重威胁青少年和儿童生命的常见恶性肿瘤。自噬是一种由自噬相关基因（ARGs）介导的细胞内代谢过程，已知其与骨肉瘤的进展和耐药性有关。在本研究中，分析了来自TARGET和基因型-组织表达（GTEx）数据库的RNA序列数据。鉴定出一种能准确预测骨肉瘤患者临床结局的六个自噬相关长链非编码RNA（ARLs）特征，并研究了免疫反应与ARLs预后特征之间的关系。此外，我们获得了在骨肉瘤组织和健康组织中差异表达的30个ARGs，并对它们进行了功能富集分析。为了筛选与预后相关的ARGs，依次应用单变量和LASSO Cox回归分析。然后，使用多变量回归分析完成ARGs预后特征的构建。基于风险系数，我们计算了风险评分并对患者进行分组。生存分析表明，高危患者预后较差。并且我们在GSE21257队列中验证了预后模型。最后，通过qRT-PCR和western blot进行验证以测量基因的表达。结果表明，自噬相关标志物模型可能为骨肉瘤提供新的治疗和诊断靶点。
