LINC03040 Expression Is Associated with Histological Fibrosis Severity in Human NAFLD: A Analysis of Public Liver Transcriptomes

Background Liver fibrosis stage is a major determinant of adverse outcomes in nonalcoholic fatty liver disease (NAFLD), a condition now largely encompassed by metabolic dysfunction-associated steatotic liver disease. We evaluated the transcript LINC03040 before annotated as C6orf223 as a candidate marker of fibrosis severity. Methods We reanalyzed raw gene-level counts and public metadata from GSE13525, comparing F4 and F0 with a DESeq2-compatible negative-binomial workflow. Stage trends were assessed with Spearman correlation and the Kruskal-Wallis test, and exploratory receiver operating characteristic analyses used 5,000 stratified bootstrap replicates. Gene-level correlations were then repeated as partial rank correlations controlling for fibrosis stage. Results LINC03040 was upregulated in F4 versus F0, although its mean abundance was low and expression was zero in 22 of 46 F0 samples and 1 of 14 F4 samples. Expression rose across F0–F4 and remained associated with stage even after controls were excluded. Correlations with COL1A1, ACTA2, TIMP1, and LOX were weak and did not survive adjustment for fibrosis stage, and LINC03040 showed no positive association with S100A8, STAT3, or CD163. Conclusions LINC03040 expression is reproducibly associated with histological fibrosis severity in this public NAFLD cohort. These data support evaluating it as a stage-associated transcript, but they do not establish cellular origin, causal function, prognostic value, or a STAT3–S100A8 mechanism. Independent validation and experimental annotation are required.