A prognostic profile of hypoxia-induced genes for localised high-grade soft tissue sarcoma

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A prognostic profile of hypoxia-induced genes for localised high-grade soft tissue sarcoma. / Aggerholm-Pedersen, Ninna; Sørensen, Brita Singers; Overgaard, Jens; Toustrup, Kasper; Bærentzen, Steen; Nielsen, Ole Steen; Maretty-Kongstad, Katja; Nordsmark, Marianne; Alsner, Jan; Safwat, Akmal.

I: B J C, Bind 115, Nr. 9, 25.10.2016, s. 1096-1104.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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@article{4aeb7c9f67434571bedc52fd7c3eac3c,
title = "A prognostic profile of hypoxia-induced genes for localised high-grade soft tissue sarcoma",
abstract = "BACKGROUND: For decades, tumour hypoxia has been pursued as a cancer treatment target. However, prognostic and predictive biomarkers are essential for the use of this target in the clinic. This study investigates the prognostic value of a hypoxia-induced gene profile in localised soft tissue sarcoma (STS).METHODS: The hypoxia-induced gene quantification was performed by real-time quantitative PCR (RT-qPCR) of formalin-fixed, paraffin-embedded tissue samples. The gene expression cut-points were determined in a test cohort of 55 STS patients and used to allocate each patient into a more or a less hypoxic group. The cut-points found in the test cohort were applied to a cohort of 77 STS patients for validation.RESULTS: For patients with localised high-grade STS treated with surgery with or without postoperative radiation therapy, the prognostic value of the hypoxia-induced gene profile was proved in the test cohort and confirmed in the validation cohort. After adjustment for confounders, the hazard ratio (HR) was 3.2 (95{\%} CI: 1.5; 7.0) for patients with more hypoxic tumours compared with patients with less hypoxic tumours regarding disease-specific survival. Moreover, for the development of metastatic disease, the HR was 2.61 (95{\%} CI: 1.27; 5.33).CONCLUSIONS: The hypoxia-induced gene profile is a validated independent prognostic marker that may help identify STS patients needing more aggressive or different adjuvant treatment.",
author = "Ninna Aggerholm-Pedersen and S{\o}rensen, {Brita Singers} and Jens Overgaard and Kasper Toustrup and Steen B{\ae}rentzen and Nielsen, {Ole Steen} and Katja Maretty-Kongstad and Marianne Nordsmark and Jan Alsner and Akmal Safwat",
year = "2016",
month = "10",
day = "25",
doi = "10.1038/bjc.2016.310",
language = "English",
volume = "115",
pages = "1096--1104",
journal = "B J C",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "9",

}

RIS

TY - JOUR

T1 - A prognostic profile of hypoxia-induced genes for localised high-grade soft tissue sarcoma

AU - Aggerholm-Pedersen, Ninna

AU - Sørensen, Brita Singers

AU - Overgaard, Jens

AU - Toustrup, Kasper

AU - Bærentzen, Steen

AU - Nielsen, Ole Steen

AU - Maretty-Kongstad, Katja

AU - Nordsmark, Marianne

AU - Alsner, Jan

AU - Safwat, Akmal

PY - 2016/10/25

Y1 - 2016/10/25

N2 - BACKGROUND: For decades, tumour hypoxia has been pursued as a cancer treatment target. However, prognostic and predictive biomarkers are essential for the use of this target in the clinic. This study investigates the prognostic value of a hypoxia-induced gene profile in localised soft tissue sarcoma (STS).METHODS: The hypoxia-induced gene quantification was performed by real-time quantitative PCR (RT-qPCR) of formalin-fixed, paraffin-embedded tissue samples. The gene expression cut-points were determined in a test cohort of 55 STS patients and used to allocate each patient into a more or a less hypoxic group. The cut-points found in the test cohort were applied to a cohort of 77 STS patients for validation.RESULTS: For patients with localised high-grade STS treated with surgery with or without postoperative radiation therapy, the prognostic value of the hypoxia-induced gene profile was proved in the test cohort and confirmed in the validation cohort. After adjustment for confounders, the hazard ratio (HR) was 3.2 (95% CI: 1.5; 7.0) for patients with more hypoxic tumours compared with patients with less hypoxic tumours regarding disease-specific survival. Moreover, for the development of metastatic disease, the HR was 2.61 (95% CI: 1.27; 5.33).CONCLUSIONS: The hypoxia-induced gene profile is a validated independent prognostic marker that may help identify STS patients needing more aggressive or different adjuvant treatment.

AB - BACKGROUND: For decades, tumour hypoxia has been pursued as a cancer treatment target. However, prognostic and predictive biomarkers are essential for the use of this target in the clinic. This study investigates the prognostic value of a hypoxia-induced gene profile in localised soft tissue sarcoma (STS).METHODS: The hypoxia-induced gene quantification was performed by real-time quantitative PCR (RT-qPCR) of formalin-fixed, paraffin-embedded tissue samples. The gene expression cut-points were determined in a test cohort of 55 STS patients and used to allocate each patient into a more or a less hypoxic group. The cut-points found in the test cohort were applied to a cohort of 77 STS patients for validation.RESULTS: For patients with localised high-grade STS treated with surgery with or without postoperative radiation therapy, the prognostic value of the hypoxia-induced gene profile was proved in the test cohort and confirmed in the validation cohort. After adjustment for confounders, the hazard ratio (HR) was 3.2 (95% CI: 1.5; 7.0) for patients with more hypoxic tumours compared with patients with less hypoxic tumours regarding disease-specific survival. Moreover, for the development of metastatic disease, the HR was 2.61 (95% CI: 1.27; 5.33).CONCLUSIONS: The hypoxia-induced gene profile is a validated independent prognostic marker that may help identify STS patients needing more aggressive or different adjuvant treatment.

U2 - 10.1038/bjc.2016.310

DO - 10.1038/bjc.2016.310

M3 - Journal article

C2 - 27701385

VL - 115

SP - 1096

EP - 1104

JO - B J C

JF - B J C

SN - 0007-0920

IS - 9

ER -