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

作者：Aggerholm Pedersen Ninna; Sorensen Brita Singers; Overgaard Jens; Toustrup Kasper; Baerentzen Steen; Nielsen Ole Steen; Maretty Kongstad Katja; Nordsmark Marianne; Alsner Jan; Safwat Akmal

来源：British Journal of Cancer, 2016, 115(9): 1096-1104.

DOI：10.1038/bjc.2016.310

• soft tissue sarcoma
• gene expression profiling
• prognostic factor
• hypoxia

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.

• 出版日期2016-10-25