Key Laboratory of Arrhythmias of the Ministry of Education of China, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
Shanghai Pudong New Area Mental Health Center, Tongji University School of Medicine, Shanghai 200124, China.
Aging (Albany NY). 2021 Mar 3;13(5):7517-7537. doi: 10.18632/aging.202615.
Hepatocellular carcinoma is one of the most fatal cancers, and the majority of patients die within three years. However, a small proportion of patients overcome this fatal disease and survive for more than five years. To determine the molecular characteristics of long-term survivors (survival ≥ 5 years), we analyzed the genomic and clinical data of hepatocellular carcinoma patients from The Cancer Genome Atlas and the International Cancer Genome Consortium databases, and identified molecular features that were strongly associated with the patients' prognosis. Genes involved in the cell cycle were expressed at lower levels in tumor tissues from long-term survivors than those from short-term survivors (survival ≤ 1 years). High levels of positive regulators of the G/S cell cycle transition (cyclin-dependent kinase 2 [], , Cyclin E2 [], , ) were potential markers of poor prognosis. Hepatocellular carcinoma patients with mutations were mainly belonged to the short-term survivor group. Abemaciclib, an FDA-approved selective inhibitor of CDK4/6, inhibited the cell proliferation and tumor growth of hepatocellular carcinoma cells and . Thus, high G/S transition-related gene levels and mutations are promising diagnostic biomarkers for short-term survivals, and abemaciclib may be a potential targeted drug for hepatocellular carcinoma.
肝细胞癌是最致命的癌症之一，大多数患者在三年内死亡。然而，有一小部分患者战胜了这种致命的疾病并存活了五年以上。为了确定长期幸存者（生存时间≥5 年）的分子特征，我们分析了来自癌症基因组图谱和国际癌症基因组联盟数据库的肝细胞癌患者的基因组和临床数据，并确定了与患者预后强烈相关的分子特征。与短期幸存者（生存时间≤1 年）相比，长期幸存者肿瘤组织中细胞周期相关基因的表达水平较低。G1/S 细胞周期转换的正调控因子（细胞周期蛋白依赖性激酶 2 [CDK2]、细胞周期蛋白 E2 [CCNE2]、）的高表达水平是预后不良的潜在标志物。发生 突变的肝细胞癌患者主要属于短期幸存者组。阿贝西利（一种 FDA 批准的 CDK4/6 选择性抑制剂）抑制了肝细胞癌细胞的增殖和肿瘤生长。因此，高 G1/S 过渡相关基因水平和 突变是短期存活的有前途的诊断生物标志物，阿贝西利可能是肝细胞癌的一种潜在靶向药物。
