Noncoding RNA Transcripts Based Molecular Phenotyping of MASLD and MASH Patients.

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive hepatic metabolic disorder characterized by excessive fat accumulation in hepatocytes. MASLD can advance to metabolic dysfunction-associated steatohepatitis (MASH). These conditions often lead to hepatic fibrosis, cirrhosis and hepatocellular carcinoma (HCC) if not timely diagnosed and managed; thus, molecular phenotyping of MASLD and MASH conditions is highly desirable. The analyses were performed to identify distinct, differentially expressed genes, particularly noncoding ones, in MASLD and MASH patient samples, thereby expanding diagnostic and therapeutic options.

METHODS

We extracted the data from a recent transcriptomic study by Govaere et al. on MASLD and MASH patient samples. We focused on transcripts with limited coding potential to broaden the scope of biomarker or therapeutic target identification, given their very specific expression patterns.

RESULTS

This analysis identified long noncoding RNAs (lncRNAs) that are differentially expressed among MASLD and MASH conditions. Among the up-regulated lncRNAs, 49 were specific to MASLD, such as MYCNOS. In contrast, 88 were unique to MASH, such as ELFN2-208, LINC01507 and LINC01435. Similarly, among the down-regulated noncoding transcripts, 93 were unique to MASLD, including AADACL2-AS1 and ST8SIA6-AS1, whereas 132 were unique to MASH, such as SYBU-AS1, LGALS17A-207, ZNF474-AS1 and LINC01116. Additionally, we employed the Genomic Regions Enrichment of Annotations Tool (GREAT) to assess their functional relevance in MASLD or MASH and to link them to biologically meaningful terms.

CONCLUSION

This study broadens the scope of noncoding RNA-based MASLD/MASH biomarker and therapeutic target identification, which ultimately aids early diagnosis of these prominent liver diseases and helps prevent advanced liver diseases such as HCC.