Authors
Siqi Luo, Diguang Wen, Jingyi Zhang, Zuojin Liu, Jiao Lu, Jianchuan Deng, Hanqing Zeng, Shifeng Lou, Yue Li, Lin Lv
Published in
International journal of genomics. Volume 2026. Pages 6542992. Epub Oct 10, 2026.
Abstract
YTHDC1 is a nuclear N6-methyladenosine reader involved in RNA processing. Its abundance, cellular distribution, and relationship with the immune microenvironment in hepatocellular carcinoma (HCC) remain incompletely characterized.
We integrated paired tumor-adjacent transcriptomic and proteomic cohorts, three single-cell RNA-sequencing datasets containing 249,080 quality-controlled cells, four outcome cohorts, three immune checkpoint inhibitor (ICI) cohorts, paired clinical specimens, and cell-based YTHDC1-knockdown assays. Patient-level analyses covered hepatocyte programs, immune states, expression-supported ligand-receptor axes, survival, ICI response, and exploratory single-cell network perturbation.
YTHDC1 protein abundance was higher in 160 paired CPTAC samples (Hedges' g = 1.21, 95% confidence interval [CI] 1.01-1.42), whereas RNA effects varied across cohorts. Single-cell analysis localized YTHDC1 across hepatic and immune compartments and identified patient-level associations with hepatocyte, lymphoid, and myeloid programs. SPP1-CD44 received the strongest cross-cohort expression support among prespecified hepatocyte-to-myeloid axes. A transferred hepatocyte state showed a pooled tumor-adjacent effect of g = 0.42 (95% CI 0.04-0.80), and higher YTHDC1 abundance was associated with poorer overall survival in study-aware univariable models (hazard ratio 1.20, 95% CI 1.06-1.36). In 37 ICI-treated patients, the pooled responder-nonresponder effect for YTHDC1 was small (g = 0.05, 95% CI -0.60 to 0.71). Exploratory virtual knockout showed modest cross-cohort agreement in network perturbation ranks. Paired clinical tissues supported increased YTHDC1 mRNA and protein abundance, and YTHDC1 silencing reduced proliferation-related readouts and THP-1 migration in two HCC cell lines.
YTHDC1 is increased at the protein level in HCC and is situated within identifiable hepatocyte and immune programs. Functional assays support its contribution to HCC cell proliferation and tumor cell-dependent macrophage-like cell migration under the tested conditions.
PMID:
42859557
Bibliographic data and abstract were imported from PubMed on 11 Oct 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 6
- Comments 0