开发和验证用于膀胱癌的新型液-液相分离基因特征。
Development and validation of a novel liquid-liquid phase separation gene signature for bladder cancer.
机构信息
Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China.
Department of Clinical Laboratory, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 201600, China.
出版信息
Sci Rep. 2024 Sep 29;14(1):22552. doi: 10.1038/s41598-024-73422-8.
Bladder carcinoma (BLCA) represents a common urinary tract malignancy, characterized by aggressive behavior and high recurrence rates. The biological response regulation during tumor proliferation and metastasis is intimately associated with liquid-liquid phase separation (LLPS). For the purpose of enhancing early detection and treatment, this study employed transcriptomic data to examine the prognostic implications of LLPS-associated genes and formulate a predictive model. Clinical and transcriptomic data of bladder cancer patients were sourced from the GEO and TCGA databases. This study applied a clustering algorithm using non-negative matrix factorization (NMF) to classify samples, which were systematically compared based on their liquid-liquid phase separation characteristics. Prognostic models were developed using multivariate Cox regression and the Least Absolute Shrinkage Selection Operator (LASSO) algorithm to establish risk formulas for nine genes. The gene signature's validity was tested across the entire TCGA cohort (406 cases), the TCGA testing cohort (120 cases), and the external validation dataset GSE13507. The predictive accuracy of the signature system was assessed using receiver operating characteristic (ROC) and Kaplan-Meier curves. Additionally, decision curve analysis incorporating clinicopathological parameters and the genetic signature was employed to predict individual survival. This study identified two distinct molecular subtypes, C1 and C2. Patients with the C1 subtype exhibited significantly better prognoses than those with the C2 subtype. Low-risk group patients consistently showed superior prognoses compared to high-risk groups across the entire TCGA, GEO, and TCGA training cohorts. Furthermore, the LLPS-related gene model demonstrated prognostic value independent of other clinical traits. This study identifies LLPS-associated gene clusters and establishes an independent, accurate prognostic model for BLCA. The model holds potential for clinical application in BLCA prognosis assessment.
膀胱癌(BLCA)是一种常见的泌尿道恶性肿瘤,其具有侵袭性的行为和高复发率。肿瘤增殖和转移过程中的生物学反应调节与液-液相分离(LLPS)密切相关。为了提高早期检测和治疗效果,本研究利用转录组数据研究了与 LLPS 相关的基因的预后意义,并构建了一个预测模型。从 GEO 和 TCGA 数据库中获取了膀胱癌患者的临床和转录组数据。本研究使用非负矩阵分解(NMF)聚类算法对样本进行分类,并根据其液-液相分离特征进行系统比较。使用多变量 Cox 回归和最小绝对收缩和选择算子(LASSO)算法构建了九个基因的风险公式,以建立预后模型。该基因特征在整个 TCGA 队列(406 例)、TCGA 测试队列(120 例)和外部验证数据集 GSE13507 中进行了验证。通过接收者操作特征(ROC)和 Kaplan-Meier 曲线评估了特征系统的预测准确性。此外,还使用包含临床病理参数和遗传特征的决策曲线分析来预测个体生存。本研究确定了两个不同的分子亚型,C1 和 C2。与 C2 亚型相比,C1 亚型的患者预后明显更好。低危组患者在整个 TCGA、GEO 和 TCGA 训练队列中均表现出比高危组更好的预后。此外,LLPS 相关基因模型显示出与其他临床特征无关的预后价值。本研究确定了与 LLPS 相关的基因簇,并建立了一个独立、准确的 BLCA 预后模型。该模型具有在 BLCA 预后评估中临床应用的潜力。