Bioinformatic analysis of molecular expression patterns during the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD)

The global incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) continues to rise, primarily driven by the escalating obesity epidemic worldwide. MASLD, a spectrum of liver disorders, can progress to more severe conditions, metabolic dysfunction-associated steatohepatitis (MASH), ultimately culminating in hepatocellular carcinoma (HCC). Given the complex nature of MASLD, there is an urgent need to develop robust risk prediction models and design specialized cancer screening initiatives tailored specifically for individuals with MASLD. This study aimed to identify genes exhibiting trending expression patterns that could serve as potential biomarkers or therapeutic targets. Our approach involved analyzing expression patterns across the five stages of MASLD development and progression. Notably, we introduced an innovative two-phase classification-MASLD occurrence and MASLD progression-instead of categorizing differentially expressed genes (DEGs) into multiple types. Leveraging LASSO regression models, we demonstrated their relatively strong capability to predict and distinguish both MASLD occurrence and progression. Furthermore, our analysis identified CYP7A1 and TNFRSF12A as significantly associated with the prognosis of MASLD progressing to HCC. These findings contribute to the understanding of gene expression dynamics in MASLD and may pave the way for the development of effective prognostic tools and targeted therapies in the realm of liver disease.