The present study was designed to update the knowledge about
hypoxia-related multi-omic molecular landscape in
hepatocellular carcinoma (HCC) tissues. Large-size HCC datasets from multiple centers were collected. The
hypoxia exposure of
tumor tissue from patients in 10 HCC cohorts was estimated using a novel HCC-specific
hypoxia score system constructed in our previous study. A comprehensive bioinformatical analysis was conducted to compare
hypoxia-associated multi-omic molecular features in patients with a high
hypoxia score to a low
hypoxia score. We found that patients with different exposure to
hypoxia differed significantly in transcriptomic, genomic, epigenomic, and proteomic alterations, including differences in
mRNA,
microRNA (miR), and
long non-coding RNA (
lncRNA) expression, differences in copy number alterations (CNAs), differences in DNA methylation levels, differences in
RNA alternative splicing events, and differences in
protein levels. HCC survival- associated molecular events were identified. The potential correlation between molecular features related to
hypoxia has also been explored, and various networks have been constructed. We revealed a particularly comprehensive
hypoxia-related molecular landscape in
tumor tissues that provided novel evidence and perspectives to explain the role of
hypoxia in HCC. Clinically, the data obtained from the present study may enable the development of individualized treatment or management strategies for HCC patients with different levels of
hypoxia exposure.