A novel signature derived from immunoregulatory and hypoxia genes predicts prognosis in liver and five other cancers
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 patient...
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| Format: | Article |
| Language: | English |
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BMC
2019-01-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12967-019-1775-9 |
| _version_ | 1818535689477685248 |
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| author | Wai Hoong Chang Donall Forde Alvina G. Lai |
| author_facet | Wai Hoong Chang Donall Forde Alvina G. Lai |
| author_sort | Wai Hoong Chang |
| collection | DOAJ |
| description | 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-infiltrating 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 five 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 sufficient and effective in predicting survival in liver and five 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 profiles increased their prognostic ability. Conclusions This study, to our knowledge, is the first to identify a gene signature uniting both tumor hypoxia and lymphocytic infiltration as a prognostic determinant in six cancer types (n = 2712). The 8-gene signature can be used for patient risk stratification by incorporating hypoxia information to aid clinical decision making. |
| first_indexed | 2024-12-11T18:28:16Z |
| format | Article |
| id | doaj.art-d20a81dcb493407e88ef60332547592c |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-11T18:28:16Z |
| publishDate | 2019-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-d20a81dcb493407e88ef60332547592c2022-12-22T00:55:00ZengBMCJournal of Translational Medicine1479-58762019-01-0117111210.1186/s12967-019-1775-9A novel signature derived from immunoregulatory and hypoxia genes predicts prognosis in liver and five other cancersWai Hoong Chang0Donall Forde1Alvina G. Lai2Nuffield Department of Medicine, University of OxfordNuffield Department of Medicine, University of OxfordNuffield Department of Medicine, University of OxfordAbstract 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-infiltrating 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 five 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 sufficient and effective in predicting survival in liver and five 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 profiles increased their prognostic ability. Conclusions This study, to our knowledge, is the first to identify a gene signature uniting both tumor hypoxia and lymphocytic infiltration as a prognostic determinant in six cancer types (n = 2712). The 8-gene signature can be used for patient risk stratification by incorporating hypoxia information to aid clinical decision making.http://link.springer.com/article/10.1186/s12967-019-1775-9HypoxiaT cellsTumor-infiltrating lymphocytesHepatocellular carcinomaPan-cancerGene signature |
| spellingShingle | Wai Hoong Chang Donall Forde Alvina G. Lai A novel signature derived from immunoregulatory and hypoxia genes predicts prognosis in liver and five other cancers Journal of Translational Medicine Hypoxia T cells Tumor-infiltrating lymphocytes Hepatocellular carcinoma Pan-cancer Gene signature |
| title | A novel signature derived from immunoregulatory and hypoxia genes predicts prognosis in liver and five other cancers |
| title_full | A novel signature derived from immunoregulatory and hypoxia genes predicts prognosis in liver and five other cancers |
| title_fullStr | A novel signature derived from immunoregulatory and hypoxia genes predicts prognosis in liver and five other cancers |
| title_full_unstemmed | A novel signature derived from immunoregulatory and hypoxia genes predicts prognosis in liver and five other cancers |
| title_short | A novel signature derived from immunoregulatory and hypoxia genes predicts prognosis in liver and five other cancers |
| title_sort | novel signature derived from immunoregulatory and hypoxia genes predicts prognosis in liver and five other cancers |
| topic | Hypoxia T cells Tumor-infiltrating lymphocytes Hepatocellular carcinoma Pan-cancer Gene signature |
| url | http://link.springer.com/article/10.1186/s12967-019-1775-9 |
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