Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou 510315, China.
Cancer Center, Southern Medical University, Guangzhou 510315, China.
Aging (Albany NY). 2024 Jun 12;16(11):10108-10131. doi: 10.18632/aging.205923.
In all mammals, the basement membrane serves as a pivotal extracellular matrix. Hepatocellular carcinoma (HCC) is a challenge among numerous cancer types shaped by basement membrane-related genes (BMGs). Our research established an innovative prognostic model that is highly accurate in its prediction of HCC prognoses and immunotherapy efficacy to summarize the crucial role of BMGs in HCC. We obtained HCC transcriptome analysis data and corresponding clinical data from The Cancer Genome Atlas (TCGA). To augment our dataset, we incorporated 222 differentially expressed BMGs identified from relevant literature. A weighted gene coexpression network analysis (WGCNA) of 10158 genes demonstrated four modules that were connected to HCC. Additionally, 66 genes that are found at the intersection of BMGs and HCC-related genes were designated as hub HCC-related BMGs. MMP1, ITGA2, P3H1, and CTSA comprise the novel model that was engineered using univariate and multivariate Cox regression analysis. Furthermore, the International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO) datasets encouraged the BMs model's validity. The overall survival (OS) of individuals with HCC may be precisely predicted in the TCGA and ICGC databases utilizing the BMs model. A nomogram based on the model was created in the TCGA database at similar time, and displayed a favorable discriminating ability for HCC. Particularly, when compared to the patients at an elevated risk, the patients with a low-risk profile presented different tumor microenvironment (TME) and hallmark pathways. Moreover, we discovered that a lower risk score of HCC patients would display a greater response to immunotherapy. Finally, quantitative real-time PCR (qRT-PCR) experiments were used to verify the expression patterns of BMs model. In summary, BMs model demonstrated efficacy in prognosticating the survival probability of HCC patients and their immunotherapeutic responsiveness.
在所有哺乳动物中,基膜作为一个关键的细胞外基质。肝细胞癌(HCC)是众多癌症类型中的一个挑战,由基膜相关基因(BMGs)塑造。我们的研究建立了一个创新的预后模型,该模型在预测 HCC 预后和免疫治疗疗效方面非常准确,总结了 BMGs 在 HCC 中的关键作用。我们从癌症基因组图谱(TCGA)中获得了 HCC 转录组分析数据和相应的临床数据。为了扩充我们的数据集,我们纳入了从相关文献中获得的 222 个差异表达的 BMGs。对 10158 个基因进行加权基因共表达网络分析(WGCNA)显示了与 HCC 相关的四个模块。此外,在 BMGs 和 HCC 相关基因的交点处发现的 66 个基因被指定为 HCC 相关 BMGs 的枢纽。使用单变量和多变量 Cox 回归分析构建了一个新的模型,其中包含 MMP1、ITGA2、P3H1 和 CTSA。此外,国际癌症基因组联合会(ICGC)和基因表达综合数据库(GEO)数据集也验证了 BMs 模型的有效性。该模型可以在 TCGA 和 ICGC 数据库中精确预测 HCC 患者的总生存期(OS)。同时,在 TCGA 数据库中创建了一个基于该模型的列线图,显示了对 HCC 良好的区分能力。特别是,与高危患者相比,低危患者的肿瘤微环境(TME)和特征途径不同。此外,我们发现 HCC 患者的风险评分较低,对免疫治疗的反应也会更大。最后,通过定量实时 PCR(qRT-PCR)实验验证了 BMs 模型的表达模式。总之,BMs 模型在预测 HCC 患者的生存概率及其免疫治疗反应方面表现出了有效性。