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应激相关基因在血细胞中的表达与接受放疗的头颈部癌症患者的预后相关。

Stress associated gene expression in blood cells is related to outcome in radiotherapy treated head and neck cancer patients.

机构信息

Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo 0316, Norway.

出版信息

BMC Cancer. 2012 Sep 25;12:426. doi: 10.1186/1471-2407-12-426.

Abstract

BACKGROUND

We previously observed that a radiotherapy-induced biochemical response in plasma was associated with favourable outcome in head and neck squamous carcinoma cancer (HNSCC) patients. The aim of the present study was to compare stress associated blood cell gene expression between two sub-groups of HNSCC patients with different biochemical responses to radiotherapy.

METHODS

Out of 87 patients (histologically verified), 10 biochemical 'responders' having a high relative increase in plasma oxidative damage and a concomitant decrease in plasma antioxidants during radiotherapy and 10 'poor-responders' were selected for gene-expression analysis and compared using gene set enrichment analysis.

RESULTS

There was a significant induction of stress-relevant gene-sets in the responders following radiotherapy compared to the poor-responders. The relevance of the involvement of similar stress associated gene expression for HNSCC cancer and radioresistance was verified using two publicly available data sets of 42 HNSCC cases and 14 controls (GEO GSE6791), and radiation resistant and radiation sensitive HNSCC xenografts (E-GEOD-9716).

CONCLUSIONS

Radiotherapy induces a systemic stress response, as revealed by induction of stress relevant gene expression in blood cells, which is associated to favourable outcome in a cohort of 87 HNSCC patients. Whether these changes in gene expression reflects a systemic effect or are biomarkers of the tumour micro-environmental status needs further study.

TRIAL REGISTRATION

Raw data are available at ArrayExpress under accession number E-MEXP-2460.

摘要

背景

我们之前观察到,血浆中放射治疗引起的生化反应与头颈部鳞状细胞癌(HNSCC)患者的良好预后相关。本研究的目的是比较两种不同放射治疗生化反应的 HNSCC 患者之间与应激相关的血液细胞基因表达。

方法

在 87 名患者(经组织学证实)中,选择了 10 名生化“ responder”(在放射治疗过程中血浆氧化损伤相对增加,同时血浆抗氧化剂减少)和 10 名“ poor-responder”进行基因表达分析,并使用基因集富集分析进行比较。

结果

与 poor-responder 相比, responder 组在放射治疗后应激相关基因集的诱导明显增加。使用两个公开的 42 个 HNSCC 病例和 14 个对照(GEO GSE6791)以及辐射抗性和辐射敏感的 HNSCC 异种移植(E-GEOD-9716)的数据集,验证了涉及类似应激相关基因表达的 HNSCC 癌症和放射抗性的相关性。

结论

放射治疗会引起全身应激反应,这表现在血液细胞中应激相关基因表达的诱导,这与 87 例 HNSCC 患者队列的良好预后相关。这些基因表达的变化是否反映了全身效应,或者是肿瘤微环境状态的生物标志物,需要进一步研究。

试验注册

原始数据可在 ArrayExpress 上以 E-MEXP-2460 的访问号获得。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed6e/3517770/e8004589f0b1/1471-2407-12-426-1.jpg

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