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Research Paper|Volume 13, Issue 5|pp 6525—6553

Hypoxia associated multi-omics molecular landscape of tumor tissue in patients with hepatocellular carcinoma

Qiangnu Zhang1,2, Lijun Qiao1,2, Quan Liu1,2, Xiangpan Kong4, Jun Hu5, Weibin Hu1,3, Zongze Wu1,3, Mingyue Li1,3, Liping Liu1,3
  • 1Department of Hepatobiliary and Pancreas Surgery, The Second Clinical Medical College, Jinan University, Shenzhen People’s Hospital, Shenzhen 518020, Guangdong, China
  • 2Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou 510632, Guangdong, China
  • 3Department of Hepatobiliary and Pancreas Surgery, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518020, China
  • 4Faculty of Science and Engineering, University of Groningen, Groningen 9747, Netherlands
  • 5Institute of Pathology, University Clinic of Heidelberg, Heidelberg 69120, Germany
* Equal contribution
Received: October 1, 2020Accepted: November 16, 2020Published: March 10, 2021
https://doi.org/10.18632/aging.202723

Copyright: © 2021 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.