Qu Meilin, Han Tao, Chen Xiaoquan, Sun Qingqing, Li Qing, Zhao Mingfang
School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China.
Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, China.
J Gastrointest Oncol. 2022 Jun;13(3):1289-1307. doi: 10.21037/jgo-22-398.
Hepatocellular carcinoma (HCC) is one of the malignant tumors with the highest morbidity and mortality worldwide, and its prognosis remains a challenge. Actinidia chinensis Planch (ACP) root has good efficacy against HCC. This study aimed to explore the link between ACP and potential targets of HCC, and to develop a novel immune-based gene signature to predict HCC patient survival.
Transcriptome data and clinical information on HCC were obtained from The Cancer Genome Atlas (TCGA; HCC: 374, normal: 50) and International Cancer Genome Consortium (ICGC) database (HCC: 243, normal: 202). Combined with the 2,483 immune-related genes from the Immport database, we used the least absolute shrinkage and selection operator (LASSO) to construct a prognostic model. Patients were divided into high-risk and low-risk groups by the median of the risk scores of the TCGA cohort. Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curves were used to estimate the predictability of the model in HCC prognosis, and carried out external validation based on ICGC cohort. We analyzed the correlation of this model with immune cells and immune checkpoint genes. Finally, molecular docking of these genes and the corresponding ACP components.
We constructed a prognostic model composed of 3 immune-related genes [epidermal growth factor (), baculoviral inhibitor of apoptosis repeat-containing protein 5 (), and secreted phosphoprotein 1 )]. And the high-risk group had a lower overall survival (OS) rate compared to the low-risk group (TCGA cohort: P=1.761e-05, ICGC cohort: P=8.716e-04). The outcomes of the AUC of ROC of prognostic risk model to predict for 1-, 2-, and 3-year OS: TCGA cohort: 0.749, 0.710, and 0.653 and ICGC cohort: 0.698, 0.736, and 0.753. Molecular docking results showed that quercetin had good binding activities with , , and , and ursolic acid (UA) and also had this feature.
Our study speculates that ACP root anti-HCC may be involved in the immune regulation of the body by targeting , and , which possess great potential and value as early warning molecules for HCC. This model may provide a reference for individualized diagnosis and treatment for HCC patients.
肝细胞癌（HCC）是全球发病率和死亡率最高的恶性肿瘤之一，其预后仍然是一个挑战。中华猕猴桃（ACP）根对HCC有良好疗效。本研究旨在探索ACP与HCC潜在靶点之间的联系，并开发一种基于免疫的新型基因特征来预测HCC患者的生存情况。
从癌症基因组图谱（TCGA；HCC：374例，正常：50例）和国际癌症基因组联盟（ICGC）数据库（HCC：243例，正常：202例）获取HCC的转录组数据和临床信息。结合来自Immport数据库的2483个免疫相关基因，我们使用最小绝对收缩和选择算子（LASSO）构建一个预后模型。根据TCGA队列风险评分的中位数将患者分为高风险和低风险组。采用Kaplan-Meier生存分析和受试者工作特征（ROC）曲线评估该模型对HCC预后的预测能力，并基于ICGC队列进行外部验证。我们分析了该模型与免疫细胞和免疫检查点基因的相关性。最后，对这些基因与相应的ACP成分进行分子对接。
我们构建了一个由3个免疫相关基因组成的预后模型[表皮生长因子（）、含杆状病毒凋亡重复蛋白5（）和分泌磷蛋白1（）]。与低风险组相比，高风险组的总生存（OS）率较低（TCGA队列：P = 1.761e - 05，ICGC队列：P = 8.716e - 04）。预后风险模型预测1年、2年和3年OS的ROC曲线下面积（AUC）结果：TCGA队列分别为0.749、0.710和0.653，ICGC队列分别为0.698、0.736和0.753。分子对接结果表明，槲皮素与、和具有良好的结合活性，熊果酸（UA）与也具有此特性。
我们的研究推测ACP根抗HCC可能通过靶向、和参与机体的免疫调节，它们作为HCC的预警分子具有巨大潜力和价值。该模型可为HCC患者的个体化诊断和治疗提供参考。
