Li Luyi, Gao Hui, Wang Danhan, Jiang Hao, Wang Hongzhu, Yu Jiajian, Jiang Xin, Huang Changjiang
Institude of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou, China.
The 2 Afflicated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, China.
Front Mol Biosci. 2021 Jul 1;8:624951. doi: 10.3389/fmolb.2021.624951. eCollection 2021.
Cervical cancer (CESC) is a gynecologic malignant tumor associated with high incidence and mortality rates because of its distinctive management complexity. Herein, we characterized the molecular features of CESC based on the metabolic gene expression profile by establishing a novel classification system and a scoring system termed as METAscore. Integrative analysis was performed on human CESC samples from TCGA dataset. Unsupervised clustering of RNA sequencing data on 2,752 formerly described metabolic genes identified three METAclusters. These METAclusters for overall survival time, immune characteristics, metabolic features, transcriptome features, and immunotherapeutic effectiveness existed distinct differences. Then we analyzed 207 DEGs among the three METAclusters and as well identified three geneclusters. Correspondingly, these three geneclusters also differently expressed among the aforementioned features, supporting the reliability of the metabolism-relevant molecular classification. Finally METAscore was constructed which emerged as an independent prognostic biomarker, related to CESC transcriptome features, metabolic features, immune characteristics, and linked to the sensitivity of immunotherapy for individual patient. These findings depicted a new classification and a scoring system in CESC based on the metabolic pattern, thereby furthering the understanding of CESC genetic signatures and aiding in the prediction of the effectiveness to anticancer immunotherapies.
宫颈癌(CESC)是一种妇科恶性肿瘤,因其独特的管理复杂性而具有较高的发病率和死亡率。在此,我们通过建立一种名为METAscore的新型分类系统和评分系统,基于代谢基因表达谱对宫颈癌的分子特征进行了表征。对来自TCGA数据集的人类宫颈癌样本进行了综合分析。对先前描述的2752个代谢基因的RNA测序数据进行无监督聚类,确定了三个META簇。这些META簇在总生存时间、免疫特征、代谢特征、转录组特征和免疫治疗效果方面存在明显差异。然后我们分析了三个META簇之间的207个差异表达基因(DEG),并确定了三个基因簇。相应地,这三个基因簇在上述特征中也有不同表达,支持了与代谢相关的分子分类的可靠性。最后构建了METAscore,它作为一种独立的预后生物标志物出现,与宫颈癌转录组特征、代谢特征、免疫特征相关,并与个体患者免疫治疗的敏感性相关。这些发现描绘了一种基于代谢模式的宫颈癌新分类和评分系统,从而进一步加深了对宫颈癌基因特征的理解,并有助于预测抗癌免疫治疗的有效性。