Chang, WH;
Forde, D;
Lai, AG;
(2019)
A novel signature derived from immunoregulatory and hypoxia genes predicts prognosis in liver and five other cancers.
Journal of Translational Medicine
, 17
, Article 14. 10.1186/s12967-019-1775-9.
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A novel signature derived from immunoregulatory and hypoxia genes predicts prognosis in liver and five other cancers.pdf - Published Version Download (1MB) | Preview |
Abstract
Background: Despite much progress in cancer research, its incidence and mortality continue to rise. A robust biomarker that would predict tumor behavior is highly desirable and could improve patient treatment and prognosis. Methods: In a retrospective bioinformatics analysis involving patients with liver cancer (n=839), we developed a prognostic signature consisting of 45 genes associated with tumor-infltrating lymphocytes and cellular responses to hypoxia. From this gene set, we were able to identify a second prognostic signature comprised of 8 genes. Its performance was further validated in fve other cancers: head and neck (n=520), renal papillary cell (n=290), lung (n=515), pancreas (n=178) and endometrial (n=370). Results: The 45-gene signature predicted overall survival in three liver cancer cohorts: hazard ratio (HR)=1.82, P=0.006; HR=1.84, P=0.008 and HR=2.67, P=0.003. Additionally, the reduced 8-gene signature was sufcient and efective in predicting survival in liver and fve other cancers: liver (HR=2.36, P=0.0003; HR=2.43, P=0.0002 and HR=3.45, P=0.0007), head and neck (HR=1.64, P=0.004), renal papillary cell (HR=2.31, P=0.04), lung (HR=1.45, P=0.03), pancreas (HR=1.96, P=0.006) and endometrial (HR=2.33, P=0.003). Receiver operating characteristic analyses demonstrated both signatures superior performance over current tumor staging parameters. Multivariate Cox regression analyses revealed that both 45-gene and 8-gene signatures were independent of other clinicopathological features in these cancers. Combining the gene signatures with somatic mutation profles increased their prognostic ability. Conclusions: This study, to our knowledge, is the frst to identify a gene signature uniting both tumor hypoxia and lymphocytic infltration as a prognostic determinant in six cancer types (n=2712). The 8-gene signature can be used for patient risk stratifcation by incorporating hypoxia information to aid clinical decision making.
| Type: | Article |
|---|---|
| Title: | A novel signature derived from immunoregulatory and hypoxia genes predicts prognosis in liver and five other cancers |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1186/s12967-019-1775-9 |
| Publisher version: | https://doi.org/10.1186/s12967-019-1775-9 |
| Language: | English |
| Additional information: | This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
| Keywords: | Hypoxia, T cells, Tumor-infltrating lymphocytes, Hepatocellular carcinoma, Pan-cancer, Gene signature |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10079651 |
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