Prognosis of Hepatocellular Carcinoma
The molecular mechanisms underlying HCC are not yet fully understood, so it is necessary to explore key factors and novel biomarkers for hepatocellular cancer (HCC) progression and prognosis. In this context, it is important to also look at cell death. Cell death is an important process in normal tissue development that occurs through three pathways: Apoptosis (programmed cell death), necrosis (death or decay of tissue), and autophagy (degradation of the cell). Misregulation of these pathways may contribute to tumorigenesis and development. Recent studies have highlighted the central role of genetic abnormalities in cancer metabolism. However, the study we are now looking at focuses on the genetic and transcriptomic features of cell death in HCC and their relationship to clinical variables, immune response, and prognosis. The study also constructs a cell death signature and prognostic nomogram for HCC as a reference for clinical management.
Hepatocellular carcinoma (HCC) is a type of cancer that affects the digestive system and is a major cause of cancer incidence and mortality worldwide. Despite recent advances in surgery, chemotherapy, and targeted therapy, some HCC patients still experience distant metastases, resulting in a poor prognosis. The molecular mechanisms underlying HCC are not yet fully understood, so it is necessary to explore key factors and novel biomarkers for HCC progression and prognosis. In this context, it is important to also look at cell death.
Cell death is an important process in normal tissue development that occurs through three pathways: Apoptosis (programmed cell death), necrosis (death or decay of tissue), and autophagy (degradation of the cell). Misregulation of these pathways may contribute to tumorigenesis and development. Recent studies have highlighted the central role of genetic abnormalities in cancer metabolism. However, the study we are now looking at focuses on the genetic and transcriptomic features of cell death in HCC and their relationship to clinical variables, immune response, and prognosis. The study also constructs a cell death signature and prognostic nomogram for HCC as a reference for clinical management.
Multi-Omics Analysis of the Impact of Apoptosis, Necrosis, and Autophagy on Hepatocellular Carcinoma (HCC)
This study is about the impact of three cell death-related pathways (apoptosis, necrosis and autophagy) on a type of liver cancer called HCC. To do this, they applied a multi-omics analysis. The researchers used data from the Cancer Genome Atlas and the Kyoto Encyclopedia of Genes and Genomes database. They analyzed the clinical data, gene expression levels, somatic mutations and copy number variations, and gene expression of patients with HCC.
Statistical methods such as Kaplan-Meier log rank tests and differential expression analysis were utilized to determine which genes affect the development and progression of HCC. They also made use of gene set variation analysis, Pearson's correlation analysis and gene set enrichment analysis to understand the impact of these genes on immune cells, ferroptosis-related genes, and mitochondrial-related pathways. Finally, they used a single-factor Cox regression and the least absolute shrinkage and selection operator (LASSO) to construct a signature related to cell death in HCC. The data was analyzed using R software and statistical significance was set at p < 0.05.
Complex Interplay between Cell Death Genes, Mutations, and Hepatocellular Carcinoma
The study investigated the relationship between cell death-related genes, genetic mutations, copy number variations, and transcriptomes with hepatocellular carcinoma (HCC). The researchers identified 137 autophagy-related genes, 136 apoptosis-related genes, and 159 necrosis-related genes from the KEGG database. A protein interaction analysis showed strong interactions between the three forms of cell death. After screening, 81 autophagy-related genes, 97 apoptosis-related genes, and 89 necroptosis-related genes were found to be mutated in HCC. The two most frequently mutated genes were apoptosis-related, TP53 and SPTA1.
Survival Analysis: Higher Values of FGA, FGG, and FGL were Associated with Unfavorable Prognosis
A survival analysis showed that the mutations of 6 genes were associated with the prognosis of HCC, including 4 apoptosis-related genes, 1 necroptosis-related gene, and 1 autophagy-related gene. The results showed that gene mutations in the apoptotic pathway led to decreased patient survival, while gene mutations in the necrosis pathway led to an increased patient survival. The results also showed that cell death-related tumor mutational burden (TMB) was associated with a shorter survival time, and was significantly associated with gender, with male patients having a higher TMB.
Copy number variations analysis showed that apoptosis-related genes had the most changes, and higher values of FGA, FGG, and FGL were associated with an unfavorable prognosis in HCC. The results also showed that radiation therapy caused changes in FGG and a low FGG was found in genomes not exposed to radiation therapy. They also provide insights into the relationship between cell death-related genes and HCC.
The study aimed to construct a cell death-related signature for HCC (hepatocellular carcinoma) by using Cox regression and LASSO method to screen genes that affect survival. 10 genes (4 apoptosis genes, 4 necroptosis genes, and 2 autophagy genes) were found to be used for the construction of the signature. Indeed, a prognostic analysis confirmed that high expression groups are correlated with poor survival. A multi-factor Cox regression analysis was performed on the signature, age and T stage, and these 3 variables were found to be the most significant for the prognosis of HCC. A nomogram was constructed based on these variables to predict the survival probability directly, and it was observed that when the cell death model had a high score, stage was high, and patient survival was poor.
Summing up
Cell death is a crucial process in normal tissue development that occurs through three pathways: apoptosis, necrosis, and autophagy.
The study investigated the relationship between cell death-related genes, genetic mutations, copy number variations, and also transcriptomes with HCC.
The study found that gene mutations in the apoptotic pathway led to decreased patient survival. In Contrast, gene mutations in the necrosis pathway led to increased patient survival.
The study constructed a cell death-related signature for HCC by using Cox regression and LASSO method and found that it was correlated with poor survival.
A nomogram was constructed using the cell death signature, age, and T stage, which was found to be the most significant for the prognosis of HCC.
The authors conclude:
In the present study, we focused on the genetic and transcriptomic characteristics of cell death in HCC, along with their relationships with clinical variables, prognosis and biological functions. Finally, we constructed a cell deathrelated signature and prognostic nomogram for HCC that could be considered a reference for clinical use.