Wu Jiasheng, He Jinru, Zhang Jiheng, Ji Hang, Wang Nan, Ma Shuai, Yan Xiuwei, Gao Xin, Du Jianyang, Liu Zhihui, Hu Shaoshan
Department of Neurosurgery, Emergency Medicine Center, Zhejiang Provincial People's Hospital, Affiliated to Hangzhou Medical College, Hangzhou, China.
Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Front Cell Dev Biol. 2022 May 17;10:887693. doi: 10.3389/fcell.2022.887693. eCollection 2022.
The epithelial-mesenchymal transition (EMT) is an important process that drives progression, metastasis, and oncology treatment resistance in cancers. Also, the adjacent non-tumor tissue may affect the biological properties of cancers and have potential prognostic implications. Our study aimed to identify EMT-related genes in LGG samples, explore their impact on the biological properties of lower grade gliomas (LGG) through the multi-omics analysis, and reveal the potential mechanism by which adjacent non-tumor tissue participated in the malignant progression of LGG. Based on the 121 differentially expressed EMT-related genes between normal samples from the GTEx database and LGG samples in the TCGA cohort, we identified two subtypes and constructed EMTsig. Because of the genetic, epigenetic, and transcriptomic heterogeneity, malignant features including clinical traits, molecular traits, metabolism, anti-tumor immunity, and stemness features were different between samples with C1 and C2. In addition, EMTsig could also quantify the EMT levels, variation in prognosis, and oncology treatment sensitivity of LGG patients. Therefore, EMTsig could assist us in developing objective diagnostic tools and in optimizing therapeutic strategies for LGG patients. Notably, with the GSVA, we found that adjacent non-tumor tissue might participate in the progression, metastasis, and formation of the tumor microenvironment in LGG. Therefore, the potential prognostic implications of adjacent non-tumor tissue should be considered when performing clinical interventions for LGG patients. Overall, our study investigated and validated the effects of EMT-related genes on the biological properties from multiple perspectives, and provided new insights into the function of adjacent non-tumor tissue in the malignant progression of LGG.
上皮-间质转化(EMT)是驱动癌症进展、转移和肿瘤治疗耐药性的重要过程。此外,邻近的非肿瘤组织可能会影响癌症的生物学特性,并具有潜在的预后意义。我们的研究旨在鉴定低级别胶质瘤(LGG)样本中与EMT相关的基因,通过多组学分析探索它们对LGG生物学特性的影响,并揭示邻近非肿瘤组织参与LGG恶性进展的潜在机制。基于GTEx数据库中的正常样本与TCGA队列中的LGG样本之间121个差异表达的EMT相关基因,我们鉴定出两个亚型并构建了EMTsig。由于基因、表观遗传和转录组的异质性,C1和C2样本之间的恶性特征(包括临床特征、分子特征、代谢、抗肿瘤免疫和干性特征)有所不同。此外,EMTsig还可以量化LGG患者的EMT水平、预后差异和肿瘤治疗敏感性。因此,EMTsig可以帮助我们开发客观的诊断工具,并优化LGG患者的治疗策略。值得注意的是,通过基因集变异分析(GSVA),我们发现邻近非肿瘤组织可能参与LGG的进展、转移和肿瘤微环境的形成。因此,在对LGG患者进行临床干预时,应考虑邻近非肿瘤组织的潜在预后意义。总体而言,我们的研究从多个角度研究并验证了EMT相关基因对生物学特性的影响,并为邻近非肿瘤组织在LGG恶性进展中的作用提供了新的见解。