Wu Shusheng, Li Mengge, Su Rixin, Shen Hao, He Yifu, Zhou Yangfan
Department of Medical Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Department of Medical Oncology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, China.
Front Surg. 2023 Jan 6;9:948371. doi: 10.3389/fsurg.2022.948371. eCollection 2022.
Recent studies have found that 5-methylcytosine (m5C) modulators are associated with the prognosis and treatment of cancer. However, the relevance of m5C modulators in sarcoma prognosis and the tumour microenvironment is unclear.
We selected 15 m5C regulators and performed unsupervised clustering to identify m5C modification patterns and differentially expressed genes associated with the m5C phenotype in The Cancer Genome Atlas (TCGA) sarcomas. The extent of immune cell infiltration in different clustering groups was explored using single-sample gene set enrichment analysis and estimation algorithms. A principal component analysis algorithm-based m5C scoring protocol was performed to assess the m5C modification patterns of individual tumors.
We identified two distinct m5C modification patterns in the TCGA sarcoma cohort, which possess different clinical outcomes and biological processes. Tumour microenvironment analysis revealed two groups of immune infiltration patterns highly consistent with m5C modification patterns, classified as immune inflammatory and immune desert types. We constructed m5C scores and found that high m5C scores were closely associated with leiomyosarcoma and other subtypes, and were associated with poorer prognosis, lower PD-L1 expression, and poorer immunotherapy outcomes. The best application was validated against the m5C database.
We constructed an m5C score for sarcoma based on the TCGA database and identified a poorer prognosis in the high m5c score group. The stability and good prognostic predictive power of the m5C score was verified by an external database. We found that sarcomas in the low m5C score group may have a better response to immunotherapy.
近期研究发现5-甲基胞嘧啶（m5C）调节剂与癌症的预后和治疗相关。然而，m5C调节剂在肉瘤预后和肿瘤微环境中的相关性尚不清楚。
我们选择了15个m5C调节因子，并进行无监督聚类，以识别癌症基因组图谱（TCGA）肉瘤中与m5C表型相关的m5C修饰模式和差异表达基因。使用单样本基因集富集分析和评估算法探索不同聚类组中免疫细胞浸润的程度。基于主成分分析算法执行m5C评分方案，以评估个体肿瘤的m5C修饰模式。
我们在TCGA肉瘤队列中识别出两种不同的m5C修饰模式，它们具有不同的临床结果和生物学过程。肿瘤微环境分析揭示了两组与m5C修饰模式高度一致的免疫浸润模式，分为免疫炎症型和免疫荒漠型。我们构建了m5C评分，发现高m5C评分与平滑肌肉瘤和其他亚型密切相关，并且与较差的预后、较低的PD-L1表达和较差的免疫治疗结果相关。通过m5C数据库验证了其最佳应用。
我们基于TCGA数据库构建了肉瘤的m5C评分，并确定高m5C评分组预后较差。外部数据库验证了m5C评分的稳定性和良好的预后预测能力。我们发现低m5C评分组的肉瘤可能对免疫治疗有更好的反应。
