目的:大多数肝细胞癌(HCC)是肝硬化的结果。在这项研究中,我们的目标是构建一个全面的诊断模型,以研究区分肝硬化和HCC的诊断标志物.
方法:基于包含肝硬化和HCC样本的多个GEO数据集,我们使用了套索回归,随机森林(RF)-递归特征消除(RFE)和接收器算子特征分析来筛选特征基因。随后,我们将这些基因整合到多变量逻辑回归模型中,并在训练和验证队列中验证了线性预测得分.ssGSEA算法用于估计样品中浸润免疫细胞的分数。最后,使用CCP算法对肝硬化患者进行分子分型.
结果:该研究鉴定了137个差异表达基因(DEG),并选择了5个重要基因(CXCL14,CAP2,FCN2,CCBE1和UBE2C)来构建诊断模型。在培训和验证队列中,模型显示曲线下面积(AUC)大于0.9,κ值约为0.9。此外,校准曲线显示观察到的发病率和预测的发病率之间非常一致.相对而言,与肝硬化相比,HCC显示浸润免疫细胞的整体下调。值得注意的是,CCBE1显示出与肿瘤免疫微环境以及与细胞死亡和细胞衰老过程相关的基因的强相关性。此外,具有高线性预测评分的肝硬化亚型在多个癌症相关通路中富集.
结论:结论:我们成功鉴定了区分肝硬化和肝细胞癌的诊断标记物,并开发了区分这两种情况的新型诊断模型.CCBE1可能在调节肿瘤微环境中发挥关键作用,细胞死亡和衰老。
OBJECTIVE: Most cases of hepatocellular carcinoma (HCC) arise as a consequence of cirrhosis. In this study, our objective is to construct a comprehensive diagnostic model that investigates the diagnostic markers distinguishing between cirrhosis and HCC.
METHODS: Based on multiple GEO datasets containing cirrhosis and HCC samples, we used lasso regression, random forest (RF)-recursive feature elimination (RFE) and receiver operator characteristic analysis to screen for characteristic genes. Subsequently, we integrated these genes into a multivariable logistic regression model and validated the linear prediction scores in both training and validation cohorts. The ssGSEA algorithm was used to estimate the fraction of infiltrating immune cells in the samples. Finally, molecular typing for patients with cirrhosis was performed using the CCP algorithm.
RESULTS: The study identified 137 differentially expressed genes (DEGs) and selected five significant genes (CXCL14, CAP2, FCN2, CCBE1 and UBE2C) to construct a diagnostic model. In both the training and validation cohorts, the model exhibited an area under the curve (AUC) greater than 0.9 and a kappa value of approximately 0.9. Additionally, the calibration curve demonstrated excellent concordance between observed and predicted incidence rates. Comparatively, HCC displayed overall downregulation of infiltrating immune cells compared to cirrhosis. Notably, CCBE1 showed strong correlations with the tumour immune microenvironment as well as genes associated with cell death and cellular ageing processes. Furthermore, cirrhosis subtypes with high linear predictive scores were enriched in multiple cancer-related pathways.
CONCLUSIONS: In conclusion, we successfully identified diagnostic markers distinguishing between cirrhosis and hepatocellular carcinoma and developed a novel diagnostic model for discriminating the two conditions. CCBE1 might exert a pivotal role in regulating the tumour microenvironment, cell death and senescence.