乙酰化模型预测患者预后并影响上皮性卵巢癌的免疫微环境浸润。
Acetylation model predicts prognosis of patients and affects immune microenvironment infiltration in epithelial ovarian carcinoma.
发表日期:2024 Jul 19
作者:
Xuan Wang, Xiaoning Li, Li Wei, Yankun Yu, Yeernaer Hazaisihan, Lin Tao, Wei Jia
来源:
Journal of Ovarian Research
摘要:
卵巢上皮癌(EOC)是一种常见的妇科恶性肿瘤。 EOC患者的预后与肿瘤微环境(TME)中的乙酰化修饰和免疫反应有关。然而,乙酰化相关基因、患者预后和肿瘤免疫微环境(TIME)之间的关系尚不清楚。我们的研究旨在调查乙酰化与肿瘤微环境之间的联系,目标是识别新的生物标志物来估计 EOC 患者的生存期。使用从肿瘤基因组图谱 (TCGA)、基因型组织表达 (GTEx) 和基因下载的数据通过表达主表(GEO),我们全面评估了 375 个卵巢癌标本中的乙酰化相关基因,并使用无监督聚类识别了分子亚型。比较三组的预后、时间、干细胞指数和功能浓度分析。通过最小绝对收缩和选择算子(LASSO)回归分析建立了基于乙酰化相关基因差异表达的风险模型,并使用GEO数据集验证了该特征的预测有效性。列线图用于预测患者的生存可能性。此外,还对不同EOC风险组的时机、肿瘤免疫功能障碍和排除(TIDE)评分、干性指数、体细胞突变和药物敏感性进行了评估。我们利用与乙酰化相关的差异表达基因的mRNA水平将其分为三类不同的集群。簇 2 (C2) 中免疫细胞浸润增加和干性评分较低的患者预后较差。免疫和肿瘤发生相关途径在簇 3 (C3) 中非常丰富。我们开发了十个差异表达的乙酰化相关基因的预后模型。 Kaplan-Meier 分析表明,高危患者的总生存期 (OS) 明显较差。此外,时间、肿瘤免疫功能障碍和排除(TIDE)评分、干性指数、肿瘤突变负荷(TMB)、免疫治疗反应和药物敏感性均与风险评分显着相关。我们的研究证明了乙酰化在肿瘤细胞中存在复杂的调节机制。经济合作委员会。乙酰化模式的评估可以为 EOC 免疫治疗提供新的治疗策略,以改善患者的预后。© 2024。作者。
Epithelial ovarian carcinoma (EOC) is a prevalent gynaecological malignancy. The prognosis of patients with EOC is related to acetylation modifications and immune responses in the tumour microenvironment (TME). However, the relationships between acetylation-related genes, patient prognosis, and the tumour immune microenvironment (TIME) are not yet understood. Our research aims to investigate the link between acetylation and the tumour microenvironment, with the goal of identifying new biomarkers for estimating survival of patients with EOC.Using data downloaded from the tumour genome atlas (TCGA), genotypic tissue expression (GTEx), and gene expression master table (GEO), we comprehensively evaluated acetylation-related genes in 375 ovarian cancer specimens and identified molecular subtypes using unsupervised clustering. The prognosis, TIME, stem cell index and functional concentration analysis were compared among the three groups. A risk model based on differential expression of acetylation-related genes was established through minimum absolute contraction and selection operator (LASSO) regression analysis, and the predictive validity of this feature was validated using GEO data sets. A nomogram is used to predict a patient's likelihood of survival. In addition, different EOC risk groups were evaluated for timing, tumour immune dysfunction and exclusion (TIDE) score, stemness index, somatic mutation, and drug sensitivity.We used the mRNA levels of the differentially expressed genes related to acetylation to classify them into three distinct clusters. Patients with increased immune cell infiltration and lower stemness scores in cluster 2 (C2) exhibited poorer prognosis. Immunity and tumourigenesis-related pathways were highly abundant in cluster 3 (C3). We developed a prognostic model for ten differentially expressed acetylation-related genes. Kaplan-Meier analysis demonstrated significantly worse overall survival (OS) in high-risk patients. Furthermore, the TIME, tumour immune dysfunction and exclusion (TIDE) score, stemness index, tumour mutation burden (TMB), immunotherapy response, and drug sensitivity all showed significant correlations with the risk scores.Our study demonstrated a complex regulatory mechanism of acetylation in EOC. The assessment of acetylation patterns could provide new therapeutic strategies for EOC immunotherapy to improve the prognosis of patients.© 2024. The Author(s).