Shi Yuanxin, Qiu Peng, Zhao Kai, Li Xiangyu, Feng Yunxiang, Deng Zhengdong, Wang Jianming
Department of Biliary and Pancreatic Surgery, Cancer Research Center Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Pediatric Surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Mol Biosci. 2023 May 23;10:1165243. doi: 10.3389/fmolb.2023.1165243. eCollection 2023.
: Cuproptosis and necroptosis represent two distinct programmed cell death modalities implicated in neoplastic progression; however, the role of combining cuproptosis and necroptosis in hepatocellular carcinoma (HCC) remains to be elucidated. : A total of 29 cuproptosis-related necroptosis genes (CRNGs) were identified, followed by an extensive analysis of their mutational characteristics, expression patterns, prognostic implications, and associations with the tumor microenvironment (TME). Subsequently, a CRNG subtype-related signature was developed, and its value of prognostic prediction, TME, and therapeutic responses in HCC were thoroughly investigated. Last, quantitative real-time PCR and Western blotting were employed for investigating the signature gene expression in 15 paired clinical tissue samples. : Two distinct CRNG subtypes were discerned, demonstrating associations between CRNG expression patterns, clinicopathological attributes, prognosis, and the TME. A CRNG subtype-related prognostic signature, subjected to external validation, was constructed, serving as an independent prognostic factor for HCC patients, indicating poor prognosis for high-risk individuals. Concurrently, the signature's correlations with an immune-suppressive TME, mutational features, stemness properties, immune checkpoint genes, chemoresistance-associated genes, and drug sensitivity were observed, signifying its utility in predicting treatment responses. Subsequently, highly accurate and clinically convenient nomograms were developed, and the signature genes were validated via quantitative real-time PCR and Western blotting, further substantiating the stability and dependability of the CRNG subtype-related prognostic signature. : Overall, this investigation presented an extensive panorama of CRNGs and developed the CRNG subtype-related prognostic signature, which holds potential for implementation in personalized treatment strategies and prognostic forecasting for HCC patients.
铜死亡和坏死性凋亡是肿瘤进展中涉及的两种不同的程序性细胞死亡方式；然而，铜死亡和坏死性凋亡联合在肝细胞癌（HCC）中的作用仍有待阐明。
共鉴定出29个与铜死亡相关的坏死性凋亡基因（CRNG），随后对其突变特征、表达模式、预后意义以及与肿瘤微环境（TME）的关联进行了广泛分析。随后开发了一种与CRNG亚型相关的特征，并对其在HCC中的预后预测、TME和治疗反应价值进行了深入研究。最后，采用定量实时PCR和蛋白质免疫印迹法检测15对临床组织样本中特征基因的表达。
识别出两种不同的CRNG亚型，表明CRNG表达模式、临床病理特征、预后和TME之间存在关联。构建了一种经过外部验证的与CRNG亚型相关的预后特征，作为HCC患者的独立预后因素，表明高危个体预后不良。同时，观察到该特征与免疫抑制性TME、突变特征、干性特性、免疫检查点基因、化疗耐药相关基因和药物敏感性的相关性，表明其在预测治疗反应方面的实用性。随后开发了高度准确且临床方便的列线图，并通过定量实时PCR和蛋白质免疫印迹法对特征基因进行了验证，进一步证实了与CRNG亚型相关预后特征的稳定性和可靠性。
总体而言，本研究展示了CRNG的广泛全景，并开发了与CRNG亚型相关的预后特征；其在HCC患者的个性化治疗策略制定及预后预测方面具有应用潜力。
