Wu Z-Y, Shi Z-Y
Department of Hand Plastic Surgery, The First People's Hospital of Linping District, Hangzhou, China.
Eur Rev Med Pharmacol Sci. 2022 Aug;26(16):5868-5883. doi: 10.26355/eurrev_202208_29526.
RNA methylation modifications, mainly including N1-methyladenosine (m1A), 5-methylcytosine (m5C), and N6-methyladenosine (m6A), are widely existed in osteosarcoma and involved in the biological processes of cancers. However, there is still no study regarding the relationship between osteosarcoma and m1A/m5C/m6A-associated long non-coding RNAs (lncRNAs).
Here, expression data of osteosarcoma from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database were retrieved to identify ER-related lncRNAs associated with the overall survival (OS) of osteosarcoma patients. Then, Lasso penalized Cox regression analysis was applied to construct a lncRNAs risk signature. Meanwhile, patients were stratified into two clusters based on the identified m1A/m5C/m6A-associated lncRNAs. The prognostic value and immune landscape of the identified signature and clusters were further evaluated.
Two m1A/m5C/m6A-associated lncRNAs were incorporated into our risk signature. The functional analyses indicated that the prognostic model was correlated with patient survival, and cancer metastasis and growth. Meanwhile, the signature model was significantly associated with the infiltration of immune cells, immune microenvironment, as well as several immune checkpoint genes. Similar results were detected for the lncRNAs clusters, which were significantly correlated with immune infiltration, cancer microenvironment, and immune-associated genes, and contributed to predicting the prognosis of patients. Moreover, our risk signature and clusters might help guide the application of immunotherapeutic drugs for osteosarcoma patients. Finally, a nomogram based on the risk score was established.
Overall, a risk signature based on two m1A/m5C/m6A-associated lncRNAs was generated and presented predictive value for the prognosis and immune landscapes of osteosarcoma patients. This signature can be further used in the development of novel therapeutic strategies for osteosarcoma.
RNA甲基化修饰主要包括N1-甲基腺苷（m1A）、5-甲基胞嘧啶（m5C）和N6-甲基腺苷（m6A），广泛存在于骨肉瘤中，并参与癌症的生物学过程。然而，关于骨肉瘤与m1A/m5C/m6A相关长链非编码RNA（lncRNA）之间的关系仍未有研究。
在此，我们从“生成有效治疗方案的治疗应用研究”（TARGET）数据库中检索骨肉瘤的表达数据，以鉴定与骨肉瘤患者总生存期（OS）相关的雌激素受体（ER）相关lncRNA。然后，应用套索惩罚Cox回归分析构建lncRNA风险特征。同时，根据鉴定出的m1A/m5C/m6A相关lncRNA将患者分为两个簇。进一步评估鉴定出的特征和簇的预后价值及免疫格局。
两个m1A/m5C/m6A相关lncRNA被纳入我们的风险特征。功能分析表明，预后模型与患者生存、癌症转移和生长相关。同时，特征模型与免疫细胞浸润、免疫微环境以及多个免疫检查点基因显著相关。lncRNA簇也检测到类似结果，其与免疫浸润、癌症微环境和免疫相关基因显著相关，并有助于预测患者预后。此外，我们的风险特征和簇可能有助于指导骨肉瘤患者免疫治疗药物的应用。最后，建立了基于风险评分的列线图。
总体而言，基于两个m1A/m5C/m6A相关lncRNA生成了一个风险特征，该特征对骨肉瘤患者的预后和免疫格局具有预测价值。这一特征可进一步用于骨肉瘤新治疗策略的开发。
