Liu Shuang, Shao Ruonan, Bu Xiaoyun, Xu Yujie, Shi Ming
Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Front Cell Dev Biol. 2021 Nov 8;9:742994. doi: 10.3389/fcell.2021.742994. eCollection 2021.
Hepatocellular carcinoma (HCC) is the second most lethal malignant tumor worldwide, with an increasing incidence and mortality. Due to general resistance to antitumor drugs, only limited therapies are currently available for advanced HCC patients, leading to a poor prognosis with a 5-year survival rate less than 20%. Pyroptosis is a type of inflammation-related programmed cell death and may become a new potential target for cancer therapy. However, the function and prognostic value of pyroptosis-related genes (PRGs) in HCC remain unknown. Here, we identified a total of 58 PRGs reported before and conducted a six-PRG signature the LASSO regression method in the GEO training cohort, and model efficacy was further validated in an external dataset. The HCC patients can be classified into two subgroups based on the median risk score. High-risk patients have significantly shorter overall survival (OS) than low-risk patients in both training and validation cohorts. Multivariable analysis indicated that the risk score was an independent prognostic factor for OS of HCC patients. Functional enrichment analysis and immune infiltration evaluation suggested that immune status was more activated in the low-risk group. In summary, PRGs can be a prediction factor for prognosis of HCC patients and targeting pyroptosis is a potential therapeutic alternative in HCC.
肝细胞癌（HCC）是全球第二大致命性恶性肿瘤，其发病率和死亡率呈上升趋势。由于对抗肿瘤药物普遍耐药，目前晚期HCC患者可用的治疗方法有限，导致预后较差，5年生存率低于20%。细胞焦亡是一种与炎症相关的程序性细胞死亡，可能成为癌症治疗的新潜在靶点。然而，细胞焦亡相关基因（PRGs）在HCC中的功能和预后价值仍不清楚。在此，我们共鉴定了之前报道的58个PRGs，并在GEO训练队列中采用LASSO回归方法构建了一个六基因特征模型，其疗效在一个外部数据集中得到进一步验证。根据中位风险评分，HCC患者可分为两个亚组。在训练和验证队列中，高风险患者的总生存期（OS）显著短于低风险患者。多变量分析表明，风险评分是HCC患者OS的独立预后因素。功能富集分析和免疫浸润评估表明，低风险组的免疫状态更活跃。总之，PRGs可作为HCC患者预后的预测因素，靶向细胞焦亡是HCC的一种潜在治疗选择。
