Gao Yuan, Liu Jia, Zhao Dexi, Diao Guanghao
Department of Hepatobiliary Surgery, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
Front Genet. 2022 Mar 18;13:857215. doi: 10.3389/fgene.2022.857215. eCollection 2022.
Hepatocellular carcinoma (HCC) is the most common primary liver cancer with poor prognosis. An optimized stratification of HCC patients to discriminate clinical benefit regarding different degrees of malignancy is urgently needed because of no effective and reliable prognostic biomarkers currently. HCC is typically characterized by rich vascular. The dysregulated vascular endothelial growth factor was proved a pivotal regulator of the development of HCC. Therefore, we investigated the capability of angiogenic factors (AFs) in stratifying patients and constructed a prognostic risk model. A total of 6 prognostic correlated AFs (, , , , and ) were screened via LASSO Cox regression, which provided the basis for developing a novel prognostic risk model. Based on the risk model, HCC patients were subdivided into high-risk and low-risk groups. Kaplan-Meier curve indicated that patients in the high-risk group have a lower survival rate compared with those in the low-risk group. The prognostic model showed good predictive efficacy, with AUCs reaching 0.802 at 1 year, 0.694 at 2 years, and 0.672 at 3 years. Univariate and multivariate cox regression analysis demonstrated that the risk score had significant prognostic value and was an independent prognostic factor for HCC. Moreover, this model also showed a good diagnostic positive rate in the ICGC-LIRI-JP and GSE144269. Finally, we demonstrated the efficacy of the AF-risk model in HCC patients following sorafenib adjuvant chemotherapy. And revealed the underlying molecular features involving tumor stemness, immune regulation, and genomic alterations associated with the risk score. Based on a large population, we established a novel prognostic model based on 6 AFs to help identify HCC patients with a greater risk of death. The model may provide a reference for better clinical management of HCC patients in the era of cancer precision medicine.
肝细胞癌(HCC)是最常见的原发性肝癌,预后较差。由于目前尚无有效且可靠的预后生物标志物,因此迫切需要对HCC患者进行优化分层,以区分不同恶性程度的临床获益情况。HCC的典型特征是血管丰富。血管内皮生长因子失调被证明是HCC发展的关键调节因子。因此,我们研究了血管生成因子(AFs)对患者进行分层的能力,并构建了一个预后风险模型。通过LASSO Cox回归筛选出总共6个与预后相关的AFs( 、 、 、 、 和 ),这为开发一种新的预后风险模型提供了依据。基于该风险模型,将HCC患者分为高风险组和低风险组。Kaplan-Meier曲线表明,高风险组患者的生存率低于低风险组。该预后模型显示出良好的预测效能,1年时的AUC为0.802,2年时为0.694,3年时为0.672。单因素和多因素cox回归分析表明,风险评分具有显著的预后价值,是HCC的独立预后因素。此外,该模型在ICGC-LIRI-JP和GSE144269中也显示出良好的诊断阳性率。最后,我们证明了AF风险模型在索拉非尼辅助化疗后的HCC患者中的疗效。并揭示了与风险评分相关的涉及肿瘤干性、免疫调节和基因组改变的潜在分子特征。基于大量人群,我们建立了一个基于6个AFs的新预后模型,以帮助识别死亡风险更高的HCC患者。该模型可为癌症精准医学时代更好地临床管理HCC患者提供参考。