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Identification and Development of a Novel 4-Gene Immune-Related Signature to Predict Osteosarcoma Prognosis
Frontiers in Molecular Biosciences ( IF 5 ) Pub Date : 2020-11-24 , DOI: 10.3389/fmolb.2020.608368
Mingde Cao , Junhui Zhang , Hualiang Xu , Zhujian Lin , Hong Chang , Yuchen Wang , Xusheng Huang , Xiang Chen , Hua Wang , Yancheng Song

Osteosarcoma (OS) is a malignant disease that develops rapidly and is associated with poor prognosis. Immunotherapy may provide new insights into clinical treatment strategies for OS. The purpose of this study was to identify immune-related genes that could predict OS prognosis. The gene expression profiles and clinical data of 84 OS patients were obtained from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. According to non-negative matrix factorization, two molecular subtypes of immune-related genes, C1 and C2, were acquired, and 597 differentially expressed genes between C1 and C2 were identified. Univariate Cox analysis was performed to get 14 genes associated with survival, and 4 genes (GJA5, APBB1IP, NPC2, and FKBP11) obtained through least absolute shrinkage and selection operator (LASSO)-Cox regression were used to construct a 4-gene signature as a prognostic risk model. The results showed that high FKBP11 expression was correlated with high risk (a risk factor), and that high GJA5, APBB1IP, or NPC2 expression was associated with low risk (protective factors). The testing cohort and entire TARGET cohort were used for internal verification, and the independent GSE21257 cohort was used for external validation. The study suggested that the model we constructed was reliable and performed well in predicting OS risk. The functional enrichment of the signature was studied through gene set enrichment analysis, and it was found that the risk score was related to the immune pathway. In summary, our comprehensive study found that the 4-gene signature could be used to predict OS prognosis, and new biomarkers of great significance for understanding the therapeutic targets of OS were identified.



中文翻译:

新型4基因免疫相关签名的鉴定和开发,以预测骨肉瘤的预后。

骨肉瘤(OS)是一种恶性疾病,发展迅速,预后差。免疫疗法可能为OS的临床治疗策略提供新的见解。这项研究的目的是确定可以预测OS预后的免疫相关基因。84例OS患者的基因表达谱和临床数据来自可产生有效治疗的治疗应用研究(TARGET)数据库。根据非负矩阵分解,获得了免疫相关基因的两个分子亚型,C1和C2,并鉴定了597个C1和C2之间差异表达的基因。进行单变量Cox分析以获取与生存相关的14个基因,以及4个基因(GJA5,APBB1IP,NPC2FKBP11通过最小绝对收缩和选择算子(LASSO)-Cox回归获得的数据用于构建4基因标记作为预后风险模型。结果表明,高FKBP11 表达与高风险(危险因素)相关,而高 GJA5,APBB1IP, 要么 NPC2表达与低风险(保护因子)有关。测试队列和整个TARGET队列用于内部验证,而独立的GSE21257队列用于外部验证。研究表明,我们构建的模型是可靠的,并且在预测OS风险方面表现良好。通过基因集富集分析研究了签名的功能富集,发现风险评分与免疫途径有关。总而言之,我们的综合研究发现4基因标记可用于预测OS的预后,并发现了对理解OS的治疗目标具有重要意义的新生物标记。

更新日期:2020-12-23
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