Li Bingyao, Che Yingkun, Zhu Puhua, Xu Yuanpeng, Yu Haibo, Li Deyu, Ding Xiangming
Henan Provincial People's Hospital, Xinxiang Medical University, Xinxiang, Henan, China.
Henan Provincial Key Medical Laboratory for Hepatobiliary and Pancreatic Diseases, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
Front Oncol. 2024 Jul 12;14:1388016. doi: 10.3389/fonc.2024.1388016. eCollection 2024.
Basement membranes (BMs) have recently emerged as significant players in cancer progression and metastasis, rendering them promising targets for potential anti-cancer therapies. Here, we aimed to develop a novel signature of basement membrane-related genes (BMRGs) for the prediction of clinical prognosis and tumor microenvironment in hepatocellular carcinoma (HCC).
The differentially expressed BMRGs were subjected to univariate Cox regression analysis to identify BMRGs with prognostic significance. A six-BMRGs risk score model was constructed using Least Absolute Shrinkage Selection Operator (LASSO) Cox regression. Furthermore, a nomogram incorporating the BMRGs score and other clinicopathological features was developed for accurate prediction of survival rate in patients with HCC.
A total of 121 differentially expressed BMRGs were screened from the TCGA HCC cohort. The functions of these BMRGs were significantly enriched in the extracellular matrix structure and signal transduction. The six-BMRGs risk score, comprising , , , , and , was established for the prediction of clinical prognosis, tumor microenvironment characteristics, and immunotherapy response in HCC. Kaplan-Meier analysis revealed that the BMRGs score-high group showed a significantly shorter overall survival than BMRGs score-low group. A nomogram showed that the BMRGs score could be used as a new effective clinical predictor and can be combined with other clinical variables to improve the prognosis of patients with HCC. Furthermore, the high BMRGs score subgroup exhibited an immunosuppressive state characterized by infiltration of macrophages and T-regulatory cells, elevated tumor immune dysfunction and exclusion (TIDE) score, as well as enhanced expression of immune checkpoints including PD-1, PD-L1, CTLA4, PD-L2, HAVCR2, and TIGIT. Finally, a multi-step analysis was conducted to identify two pivotal hub genes, and , in the high-scoring group of BMRGs, which exhibited significant associations with an unfavorable prognosis in HCC.
Our study suggests that the BMRGs score can serve as a robust biomarker for predicting clinical outcomes and evaluating the tumor microenvironment in patients with HCC, thereby facilitating more effective clinical implementation of immunotherapy.
基底膜（BMs）最近已成为癌症进展和转移的重要参与者，使其成为潜在抗癌治疗的有希望的靶点。在此，我们旨在开发一种新的基底膜相关基因（BMRGs）特征，用于预测肝细胞癌（HCC）的临床预后和肿瘤微环境。
对差异表达的BMRGs进行单变量Cox回归分析，以鉴定具有预后意义的BMRGs。使用最小绝对收缩选择算子（LASSO）Cox回归构建六BMRGs风险评分模型。此外，开发了一种结合BMRGs评分和其他临床病理特征的列线图，用于准确预测HCC患者的生存率。
从TCGA HCC队列中筛选出总共121个差异表达的BMRGs。这些BMRGs的功能在细胞外基质结构和信号转导中显著富集。建立了由 、 、 、 、 和 组成的六BMRGs风险评分，用于预测HCC的临床预后、肿瘤微环境特征和免疫治疗反应。Kaplan-Meier分析显示，BMRGs评分高的组总生存期明显短于BMRGs评分低的组。列线图显示，BMRGs评分可作为一种新的有效临床预测指标，并可与其他临床变量相结合，以改善HCC患者的预后。此外，高BMRGs评分亚组表现出免疫抑制状态，其特征为巨噬细胞和T调节细胞浸润、肿瘤免疫功能障碍和排斥（TIDE）评分升高，以及包括PD-1、PD-L1、CTLA4、PD-L2、HAVCR2和TIGIT在内的免疫检查点表达增强。最后，进行了多步骤分析，以鉴定BMRGs高分组中的两个关键枢纽基因 和 ，它们与HCC的不良预后显著相关。
我们的研究表明，BMRGs评分可作为预测HCC患者临床结局和评估肿瘤微环境的有力生物标志物，从而促进免疫治疗在临床上更有效的实施。
