Wang Tao, Li Wenxuan, Wu Yuelan, You Liping, Zheng Chao, Zhang Jinghao, Qu Lihong, Sun Xuehua
Department of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Department of Infectious Diseases, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
Biol Direct. 2024 Dec 19;19(1):128. doi: 10.1186/s13062-024-00569-9.
Disulfidptosis, identified as an innovative form of cellular death subsequent to cuproptosis, is currently under investigation for its mechanisms in oncological contexts. In-depth analyses exploring the relationship between disulfidptosis-related genes (DRGs) and hepatocellular carcinoma (HCC) are currently limited.
Transcriptomic data and clinical information were retrieved from the TCGA and GEO databases (GSE76427 and GSE54236), concentrating on the expression levels of 24 DRGs. Subsequently, multifactor and LASSO regression analyses were utilized to construct the 5-DRG prognostic signature. Immunohistochemistry (IHC) was employed to assess Cyclin A2 (CCNA2) protein expression levels. Quantitative real-time PCR (qRT-PCR) and western blot analyses were conducted to detect transcriptomic and protein expression of CCNA2-targeting short interfering RNA (siRNA). The Cell Counting Kit-8 (CCK-8) assay, EdU staining, and scratch experiments were employed to observe the proliferation and migration of hepatoma cell lines subsequent to CCNA2 inhibition.
Three HCC patterns were identified, among which pattern B exhibited the the most unfavorable survival outcomes. Five DRGs (STC2, PBK, CCNA2, SERPINE1, and SLC6A1) were involved to establish the 5-DRG prognostic signature. High-risk groups (HRGs) exhibited prolonged survival durations in comparison to low-risk groups (LRGs). Both bioinformatics analyses and experimental methodologies corroborated the association of CCNA2 with poor prognosis in HCC patients. Functional studies elucidated that interference with CCNA2 significantly inhibited proliferation and migration, while simultaneously promoting apoptosis in hepatoma cells and resulting in the downregulation of epithelial-mesenchymal transition (EMT)-related protein markers.
The 5-DRG prognostic signature is proficient in predicting clinical outcomes, informing therapeutic strategies, and elucidating the characteristics of the immune microenvironment in HCC patients. Furthermore, this study elucidates the potential of CCNA2 as an innovative biomarker for HCC.
二硫化物诱导的细胞死亡被认为是继铜死亡之后一种新的细胞死亡形式，目前正在研究其在肿瘤学背景下的机制。目前，关于二硫化物诱导的细胞死亡相关基因（DRGs）与肝细胞癌（HCC）之间关系的深入分析较为有限。
从TCGA和GEO数据库（GSE76427和GSE54236）中检索转录组数据和临床信息，重点关注24个DRGs的表达水平。随后，利用多因素和LASSO回归分析构建5-DRG预后特征。采用免疫组织化学（IHC）评估细胞周期蛋白A2（CCNA2）蛋白表达水平。进行定量实时PCR（qRT-PCR）和蛋白质印迹分析，以检测靶向CCNA2的小干扰RNA（siRNA）的转录组和蛋白质表达。采用细胞计数试剂盒-8（CCK-8）检测、EdU染色和划痕实验观察CCNA2抑制后肝癌细胞系的增殖和迁移。
确定了三种肝癌模式，其中模式B的生存结果最不利。五个DRGs（STC2、PBK、CCNA2、SERPINE1和SLC6A1）参与构建5-DRG预后特征。与低风险组（LRGs）相比，高风险组（HRGs）的生存时间延长。生物信息学分析和实验方法均证实CCNA2与HCC患者的不良预后相关。功能研究表明，干扰CCNA2可显著抑制肝癌细胞的增殖和迁移，同时促进其凋亡，并导致上皮-间质转化（EMT）相关蛋白标志物的下调。
5-DRG预后特征能够有效地预测HCC患者的临床结局，为治疗策略提供依据，并阐明其免疫微环境特征。此外，本研究阐明了CCNA2作为HCC创新生物标志物的潜力。
