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A novel hypoxia gene signature indicates prognosis and immune microenvironments characters in patients with hepatocellular carcinoma |
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| Authors: | Qiangnu Zhang Lijun Qiao Juan Liao Quan Liu Pengyu Liu Liping Liu |
| Affiliation: | 1. Department of Hepatobiliary and Pancreas Surgery, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital), Shenzhen, Guangdong, China Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, China Contribution: Data curation (lead), Formal analysis (lead), Investigation (lead), Methodology (lead), Visualization (lead), Writing - original draft (lead);2. Department of Hepatobiliary and Pancreas Surgery, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital), Shenzhen, Guangdong, China Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, China Contribution: Conceptualization (equal), Funding acquisition (equal), Investigation (equal), Methodology (equal), Writing - original draft (equal);3. Department of Gastroenterology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China;4. Department of Hepatobiliary and Pancreas Surgery, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital), Shenzhen, Guangdong, China Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, China Contribution: Methodology (equal), Visualization (equal), Writing - review & editing (equal);5. Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, NY, USA Contribution: Data curation (equal), Investigation (equal), Writing - original draft (equal);6. Department of Hepatobiliary and Pancreas Surgery, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital), Shenzhen, Guangdong, China |
| Abstract: | Due to the lack of a suitable gene signature, it is difficult to assess the hypoxic exposure of HCC tissues. The clinical value of assessing hypoxia in HCC is short of tissue-level evidence. We tried to establish a robust and HCC-suitable hypoxia signature using microarray analysis and a robust rank aggregation algorithm. Based on the hypoxia signature, we obtained a hypoxia-associated HCC subtypes system using unsupervised hierarchical clustering and a hypoxia score system was provided using gene set variation analysis. A novel signature containing 21 stable hypoxia-related genes was constructed to effectively indicate the exposure of hypoxia in HCC tissues. The signature was validated by qRT-PCR and compared with other published hypoxia signatures in multiple large-size HCC cohorts. The subtype of HCC derived from this signature had different prognosis and other clinical characteristics. The hypoxia score obtained from the signature could be used to indicate clinical characteristics and predict prognoses of HCC patients. Moreover, we reveal a landscape of immune microenvironments in patients with different hypoxia score. In conclusion, we identified a novel HCC-suitable 21-gene hypoxia signature that could be used to estimate the hypoxia exposure in HCC tissues and indicated prognosis and a series of important clinical features in HCCs. It may enable the development of personalized counselling or treatment strategies for HCC patients with different levels of hypoxia exposure. |
| Keywords: | gene signature HCC hypoxia microenvironment prognosis |