School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China.
The First Clinical School, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
Biomolecules. 2023 Feb 14;13(2):360. doi: 10.3390/biom13020360.
Hepatocellular carcinoma (HCC) remains a global medical problem. Programmed cell death protein 1 (PD-1) is a powerful weapon against many cancers, but it is not sensitive to some patients with HCC. We obtained datasets from the Gene Expression Omnibus (GEO) database on HCC patients and PD-1 immunotherapy to select seven intersecting DEGs. Through Lasso regression, two intersecting genes were acquired as predictors of HCC and PD-1 treatment prognosis, including HAMP and FOS. Logistic regression was performed to build a prediction model. HAMP had a better ability to diagnose HCC and predict PD1 treatment sensitivity. Further, we adapted the support vector machine (SVM) technique using HAMP to predict triple-classified outcomes after PD1 treatment in HCC patients, which had an excellent classification ability. We also performed external validation using TCGA data, which showed that HAMP was elevated in the early stage of HCC. HAMP was positively correlated with the infiltration of 18 major immune cells and the expression of 2 important immune checkpoints, PDCD1 and CTLA4. We discovered a biomarker that can be used for the early diagnosis, prognosis and PD1 immunotherapy efficacy prediction of HCC for the first time and developed a diagnostic model, prognostic model and prediction model of PD1 treatment sensitivity and treatment outcome for HCC patients accordingly.
肝细胞癌（HCC）仍然是一个全球性的医学问题。程序性死亡蛋白 1（PD-1）是对抗许多癌症的有力武器，但对一些 HCC 患者并不敏感。我们从 HCC 患者和 PD-1 免疫治疗的基因表达综合数据库（GEO）中获取数据集，以选择七个相交的 DEGs。通过 Lasso 回归，获得了两个相交的基因作为 HCC 和 PD-1 治疗预后的预测因子，包括 HAMP 和 FOS。进行了逻辑回归以建立预测模型。HAMP 具有更好的诊断 HCC 和预测 PD1 治疗敏感性的能力。此外，我们使用 HAMP 采用支持向量机（SVM）技术来预测 HCC 患者接受 PD1 治疗后的三分类结果，该技术具有出色的分类能力。我们还使用 TCGA 数据进行了外部验证，结果表明 HAMP 在 HCC 的早期阶段升高。HAMP 与 18 种主要免疫细胞的浸润以及 2 种重要免疫检查点 PDCD1 和 CTLA4 的表达呈正相关。我们首次发现了一种可用于 HCC 的早期诊断、预后和 PD1 免疫治疗疗效预测的生物标志物，并开发了相应的 HCC 患者 PD1 治疗敏感性和治疗结果的诊断模型、预后模型和预测模型。
