Zhang Lanlan, Chen Xiaomin, Guo Xiangchai, Shen Huajuan, Qiu Danying, Jin Weiqun, Hou Dongjie
Nursing Division, Zhejiang Provincial People's Hospital, Hangzhou Medical College, China.
Plastic & Reconstructive Surgery Center, Department of Hand and Reconstructive Surgery, Zhejiang Provincial People's Hospital, Hangzhou Medical College, China.
Adv Clin Exp Med. 2023 Feb;32(2):233-244. doi: 10.17219/acem/152737.
Hepatocellular carcinoma (HCC) is a common tumor of the digestive system. Cell death is an essential process in normal tissue that consists of 3 classical pathways: apoptosis, necrosis and autophagy.
To perform a comprehensive analysis of the impact of cell death on liver cancer.
The Kyoto Encyclopedia of Genes and Genomes (KEGG) database and the Cancer Genome Atlas (TCGA) datasets were used to analyze the relationships between mutations in cell death-related genes and clinical variables of HCC. Then, we applied the DESeq2 package to identify aberrantly expressed genes in HCC and their related biological functions through a Pearson correlation analysis. Finally, a cell death-related signature of HCC was constructed using the single-factor Cox regression.
We identified the genes involved in apoptosis, necrosis and autophagy, of which TP53 and SPTA1 had the highest frequency of mutations. The results revealed that cell death-related tumor mutational burden (TMB) was significant for the pathologic stage and had a strong relationship with the prognosis. Moreover, 53 cell death-related genes that are differentially expressed in HCC were screened, and 3 of them were correlated with HCC prognosis. Harvey rat sarcoma viral oncogene homolog (HRAS) affected the infiltration of immune cells and was closely correlated with ferroptosis. Peptidylprolyl isomerase A (PPIA) played a significant role in mitochondrial pathways. At last, we constructed a cell death-related signature of HCC using 10 prognosis-related genes and a nomogram based on 3 variables (expression, group and stage).
This study provided a comprehensive analysis of cell death-related genes in HCC based on multi-omics data, identified the contribution of each variable to clinical outcome and predicted the survival probability of HCC patients more directly.
肝细胞癌（HCC）是消化系统常见肿瘤。细胞死亡是正常组织中的一个重要过程，包括3种经典途径：凋亡、坏死和自噬。
对细胞死亡对肝癌的影响进行全面分析。
利用京都基因与基因组百科全书（KEGG）数据库和癌症基因组图谱（TCGA）数据集分析细胞死亡相关基因的突变与HCC临床变量之间的关系。然后，应用DESeq2软件包通过Pearson相关分析识别HCC中异常表达的基因及其相关生物学功能。最后，使用单因素Cox回归构建HCC细胞死亡相关特征。
我们鉴定了参与凋亡、坏死和自噬的基因，其中TP53和SPTA1的突变频率最高。结果显示，细胞死亡相关的肿瘤突变负荷（TMB）对病理分期具有显著意义，且与预后密切相关。此外，筛选出53个在HCC中差异表达的细胞死亡相关基因，其中3个与HCC预后相关。哈维大鼠肉瘤病毒癌基因同源物（HRAS）影响免疫细胞浸润，与铁死亡密切相关。肽基脯氨酰异构酶A（PPIA）在线粒体途径中起重要作用。最后，我们利用10个预后相关基因构建了HCC细胞死亡相关特征，并基于3个变量（表达、分组和分期）构建了列线图。
本研究基于多组学数据对HCC中细胞死亡相关基因进行了全面分析，确定了各变量对临床结局的贡献，并更直接地预测了HCC患者的生存概率。
