2025/06/25 by Chunye Zhang, Yuxiang Sui, Shuai Liu +1 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Endoplasmic Reticulum Stress and Disease #Ferroptosis and cancer prognosis #Liver Disease Diagnosis and Treatment
paper · pdf · doi:10.1016/j.premed.2025.100012
openalex publication_date 2025/06/25 · openalex created_date 2025/10/10 · openalex updated_date 2026/06/27
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Patients with metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), and liver fibrosis have a high risk for HCC development. Meanwhile, MASLD and MASH are commonly associated with other metabolic diseases such as diabetes, cardiovascular disease, and obesity, accelerating the risk of HCC development. Thus, new biomarkers are needed for rapid detection and predicting the prognosis of HCC, as well as the selection of effective therapeutic targets. Currently, the molecular drivers from MASLD-MASH-liver fibrosis to HCC progression remain uncovered. To better understand the molecular mechanisms underlying the transition of MASLD-MASH-liver fibrosis to HCC, we performed a comprehensive study using multiple bioinformatic methods and machine learning strategies with different "omic" analyses, such as genomics and transcriptomics from clinical samples provided by GeneCards, DAVID, TCGA, and CPTAC, to decipher these questions. We first investigated the shared genes of these diseases and analyzed their signaling networks and the enrichment of biological functionality. Then, we identified the key hub genes that play essential roles in MASLD/MASH/liver fibrosis and HCC. Followed by an investigation into the clinical impacts of identified hub genes ( VEGFA , MMP9 , PPARG , JUN , ESR1 , and IGF1 ) in the survival prognosis of HCC patients, we analyzed the mRNA and proteomic expression levels of 6 key hub genes in normal and HCC clinical samples and their association with immune cell infiltration in the HCC tumor microenvironment. Overall, our results identified that 6 key genes play important roles in the progression of MASLD-MASH-fibrosis to HCC and the prediction of HCC prognosis in patients.