新医学2025，Vol.56Issue(1)：3-19,17.DOI:10.12464/j.issn.0253-9802.2024-0479
卵巢癌乳酸化修饰亚型的鉴定及预后评分模型构建与免疫疗效预测
Identification of lactylation-related subtypes,construction of prognostic scoring model and immunotherapy prediction in ovarian cancer
摘要
Abstract
Objective To identify lactylation-related molecular subtypes,construct a prognostic model,and predict immunotherapy efficacy in ovarian cancer(OC).Methods The prognostic significance of lactylation-related genes(LRGs)was analyzed using data from TCGA-OV,GSE63885,and GSE26193 datasets.Unsupervised clustering identified four distinct lactylation-related clusters(LRGClusters).Differential expression and Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed for these clusters.Using univariate Cox regression analysis(P＜0.0001),five prognostic-related genes(PRGs)were identified.The expression levels of these PRGs in normal ovarian tissues,as well as early and advanced-stage ovarian cancer tissues were validated via RT-qPCR.Based on the five PRGs,a second round of unsupervised clustering was conducted to identify two gene clusters(geneClusters),and a prognostic scoring system,termed LactyScore,was developed.Immune cell infiltration,immunotherapy response,and drug sensitivity analyses were then performed based on LactyScore stratification.Results Four LRGClusters and two geneClusters were identified.Five differentially expressed genes including COL16A1,SPEN,AHDC1,LUZP1,and SDF2L1 were significantly associated with prognosis of OC patients.RT-qPCR indicated that SPEN,COL16A1,AHDC1,and LUZP1 were the potential risk factors for poor prognosis,whereas SDF2L1 might serve as a protective factor.Based on these PRGs,the LactyScore prognostic scoring system was established.Survival analysis revealed that patients in the high LactyScore group exhibited significantly better overall survival compared to those in the low LactyScore group.Moreover,patients with a high LactyScore showed increased immune evasion potential and lower response rates to immunotherapy.Conclusions Five prognostic genes including COL16A1,SPEN,AHDC1,LUZP1,and SDF2L1 are associated with OC and these genes demonstrate their potential as biomarkers for OC.Furthermore,the development of the robust LactyScore system offers an accurate tool for predicting OC prognosis and immunotherapy responsiveness,providing insights for personalized therapeutic strategies.关键词
卵巢癌/乳酸化修饰/预后评分模型/免疫治疗Key words
Ovarian cancer/Lactylation/Prognostic scoring model/Immunotherapy引用本文复制引用
林子丹,周琛斐,黄舒婷,巢锦瑜,何善阳..卵巢癌乳酸化修饰亚型的鉴定及预后评分模型构建与免疫疗效预测[J].新医学,2025,56(1):3-19,17.基金项目
国家自然科学基金(82272850) （82272850）
广东省自然科学基金(2024A1515010596) （2024A1515010596）
国家卫生健康委医药卫生科技发展研究中心基金(WKZX2023CX130001) （WKZX2023CX130001）
