Validation of a hypoxia related gene signature in multiple soft tissue sarcoma cohorts
| العنوان: | Validation of a hypoxia related gene signature in multiple soft tissue sarcoma cohorts |
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| المؤلفون: | Yang, Lingjian, Forker, Laura, Irlam, Joely, Pillay, Nischalan, Choudhury, Ananya, West, Catharine |
| المصدر: | Oncotarget Yang, L, Forker, L, Irlam, J, Pillay, N, Choudhury, A & West, C 2017, ' Validation of a hypoxia related gene signature in multiple soft tissue sarcoma cohorts ', Oncotarget, vol. 9, pp. 3946-3955 . https://doi.org/10.18632/oncotarget.23280Test |
| بيانات النشر: | Impact Journals LLC, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | tumor hypoxia, gene expression signature, Soft tissue sarcoma, Prognostic biomarker, Tumor hypoxia, Manchester Cancer Research Centre, ResearchInstitutes_Networks_Beacons/mcrc, soft tissue sarcoma, prognostic biomarker, Research Paper |
| الوصف: | PURPOSE: There is a need for adjuvant/neo-adjuvant treatment strategies to prevent metastatic relapse in soft tissue sarcoma (STS). Tumor hypoxia is associated with a high-risk of metastasis and is potentially targetable. This study aimed to derive and validate a hypoxia mRNA signature for STS for future biomarker-driven trials of hypoxia targeted therapy.PATIENTS AND METHODS: RNA sequencing was used to identify seed genes induced by hypoxia in seven STS cell lines. Primary tumors in a training cohort (French training) were clustered into two phenotypes by seed gene expression and a de novo hypoxia signature derived. Prognostic significance of the de novo signature was evaluated in the training and two independent validation (French validation and The Cancer Genome Atlas) cohorts. RESULTS: 37 genes were up-regulated by hypoxia in all seven cell lines, and a 24-gene signature was derived. The high-hypoxia phenotype defined by the signature was enriched for well-established hypoxia genes reported in the literature. The signature was prognostic in univariable analysis, and in multivariable analysis in the training (n=183, HR 2.16, P=0.0054) and two independent validation (n=127, HR 3.06, P=0.0019; n=258, HR 2.05, P=0.0098) cohorts. Combining information from the hypoxia signature and a genome instability signature significantly improved prognostication. Transcriptomic analyses showed high-hypoxia tumors had more genome instability and lower immune scores. CONCLUSION: A 24-gene STS-specific hypoxia signature may be useful for prognostication and identifying patients for hypoxia-targeted therapy in clinical trials. |
| اللغة: | English |
| تدمد: | 1949-2553 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::15669d7ea52824b5aac57d9544eedabeTest http://europepmc.org/articles/PMC5790513Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.pmid.dedup....15669d7ea52824b5aac57d9544eedabe |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19492553 |
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