Integrated
Exploration of Epigenetic Dysregulation
Reveals a Stemness/EMT Subtype and MMP12 Linked to the Progression
and Prognosis in Hepatocellular Carcinoma
posted on 2024-04-23, 14:14authored byAnning Zuo, Jinyu Li, Siyuan Weng, Hui Xu, Yuyuan Zhang, Libo Wang, Zhe Xing, Peng Luo, Quan Cheng, Jing Li, Xinwei Han, Zaoqu Liu
Epigenetic dysregulation drives aberrant transcriptional
programs
playing a critical role in hepatocellular carcinoma (HCC), which may
provide novel insights into the heterogeneity of HCC. This study performed
an integrated exploration on the epigenetic dysregulation of miRNA
and methylation. We discovered and validated three patterns endowed
with gene-related transcriptional traits and clinical outcomes. Specially,
a stemness/epithelial–mesenchymal transition (EMT) subtype
was featured by immune exhaustion and the worst prognosis. Besides,
MMP12, a characteristic gene, was highly expressed in the stemness/EMT
subtype, which was verified as a pivotal regulator linked to the unfavorable
prognosis and further proven to promote tumor proliferation, invasion,
and metastasis in vitro experiments. Proteomic analysis by mass spectrometry
sequencing also indicated that the overexpression of MMP12 was significantly
associated with cell proliferation and adhesion. Taken together, this
study unveils innovative insights into epigenetic dysregulation and
identifies a stemness/EMT subtype-specific gene, MMP12, correlated
with the progression and prognosis of HCC.