Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No.3 Qingchun East Road, Shangcheng District, Hangzhou, 310016, People's Republic of China.
Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, No.3 Qingchun East Road, Shangcheng District, Hangzhou, 310016, People's Republic of China.
Reprod Sci. 2024 Feb;31(2):514-531. doi: 10.1007/s43032-023-01364-z. Epub 2023 Sep 25.
Recently, studies on the mechanisms underlying lipid metabolic reprogramming in cancer have increased. However, its significance in cervical cancer remains unclear. In the present study, a prognostic signature was constructed for patients with cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) using the expression profiles of lipid metabolism-related genes (LMRGs). Furthermore, using various bioinformatics methods, a prognostic gene signature was developed for progression-free survival (PFS). This signature was externally validated using a cervical cancer dataset (GSE44001). The characteristics of the molecular subgroups of LMRGs were analyzed, and target LMRGs were identified via differential gene analysis of the expression profiles and weighted gene correlation network analysis. Thereafter, the identified target genes were used to develop the prognostic gene signature using univariate, least absolute shrinkage and selection operator, and multivariate Cox regression analyses. The performance of the LMRG signature was evaluated using Kaplan-Meier curves, time-dependent receiver operating characteristic curves, decision curve analysis, mutation landscapes, gene set enrichment analysis, and immune score calculation. As a result, a novel eight-LMRG signature comprising ALDH3B2, CERS3, FA2H, GLTP, NR1H3, PLIN3, SLC44A3, and SQLE was constructed. Using this gene signature, patients with CESC and significantly distinguished PFS were divided. This eight-LMRG signature exhibited independent prognostic potential and superior predictive performance compared with a previously developed 12-gene signature. Our findings suggest that our novel eight-LMRG signature contributes to the implementation of precision medicine strategies for managing patients with cervical cancer by facilitating CESC prognosis.
最近，有关癌症中脂质代谢重编程机制的研究有所增加。然而，其在宫颈癌中的意义尚不清楚。在本研究中，使用脂质代谢相关基因（LMRG）的表达谱构建了宫颈鳞状细胞癌和宫颈内膜腺癌（CESC）患者的预后签名。此外，使用各种生物信息学方法，为无进展生存期（PFS）开发了预后基因签名。使用宫颈癌数据集（GSE44001）对该签名进行了外部验证。分析了 LMRG 分子亚群的特征，并通过差异基因分析表达谱和加权基因相关网络分析鉴定了靶 LMRG。此后，使用单变量、最小绝对值收缩和选择算子以及多变量 Cox 回归分析，使用鉴定出的靶基因开发了预后基因签名。使用 Kaplan-Meier 曲线、时间依赖性接收者操作特征曲线、决策曲线分析、突变景观、基因集富集分析和免疫评分计算评估了 LMRG 签名的性能。结果，构建了一个由 ALDH3B2、CERS3、FA2H、GLTP、NR1H3、PLIN3、SLC44A3 和 SQLE 组成的新的八个 LMRG 签名。使用该基因签名，可以区分 CESC 和显著区分 PFS 的患者。该八个 LMRG 签名表现出独立的预后潜力，并且与先前开发的 12 个基因签名相比具有更高的预测性能。我们的研究结果表明，我们的新八个 LMRG 签名通过促进 CESC 预后，有助于实施针对宫颈癌患者的精准医学策略。
