DNA repair pathways to regulate response to chemoradiotherapy in patients with locally advanced head and neck cancer
DNA repair pathways to regulate response to chemoradiotherapy in patients with locally advanced head and neck cancer
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DOI：
10.1007/s13277-016-5149-0
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发表时间：
2016-10-01
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影响因子：
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通讯作者：
Rosell, R.
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文献类型：
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作者：
Cirauqui, B.;Margeli, M.;Rosell, R.
含铂化疗（CRT）是局部晚期头颈癌（HNC）的首选标准治疗。然而，生存获益很小，具有大量毒性和CRT抵抗的生物标志物，可以指导治疗选择和避免发病。实体瘤中DNA修复的增加可能有助于癌细胞在治疗所提供的遗传毒性应激环境中存活的能力。我们评估了DNA修复相关基因BRCA 1，RAP 80，53结合蛋白1（53 BP 1），DNA损伤检查点1（MDC 1）和RNF 8的mRNA表达水平。我们将我们的研究结果与72例接受每周卡铂AUC 2和放疗的头颈部患者的反应和总生存率相关联。CRT的完全缓解（CR）在53 BP 1水平低的患者中为50%，而在53 BP 1水平高的患者中为6.3%（p = 0.0059）。BRCA 1 mRNA高表达者中，41.2%的患者CR，而低表达者中CR为29.4%（p = 0.72）。对于一小群53 BP 1低而BRCA 1或RAP 80高的患者，CR分别为66.7%和71.4%。低53 BP 1患者的总生存率（OS）有更好的趋势（15 vs 8 m; p = 0.056）。我们的研究结果强调了53 BP 1 mRNA作为放化疗治疗HNC患者的反应和总生存率的预测生物标志物的潜在用途。那些53 BP 1高表达的人只能从治疗中获得微薄的益处。BRCA 1和RAP 80的联合应用可进一步强化53 BP 1的预测价值。尽管这是一项样本量较小的回顾性研究，但它可以为HNC中更大规模的转化研究提供信息。
Platinum-based chemoradiotherapy (CRT) is a preferred standard of care for locally advanced head and neck cancer (HNC). However, survival benefit is small, with substantial toxicity and biomarkers of CRT resistance that could guide treatment selection and spare morbidity. Increased DNA repair in solid tumors may contribute to cancer cells' ability to survive in genotoxic stress environments afforded by therapy. We assessed mRNA expression levels of DNA repair-related genes BRCA1, RAP80, 53 binding protein 1 (53BP1), mediator of DNA damage checkpoint 1 (MDC1), and RNF8. We correlated our findings with response and overall survival in 72 head and neck patients treated with weekly carboplatin AUC 2 and radiotherapy. Complete response (CR) to CRT was 50 % in patients with low levels of 53BP1 compared to 6.3 % in patients with high levels (p = 0.0059). Of high BRCA1 mRNA expressors, 41.2 % had CR compared to 29.4 % of low expressors (p = 0.72). For a small group of patients with low 53BP1 and either high BRCA1 or RAP80, CRs were 66.7 and 71.4 %, respectively. A trend for better overall survival (OS) was found for patients with low 53BP1 (15 vs 8 m; p = 0.056). Our findings highlight the potential usefulness of 53BP1 mRNA as a predictive biomarker of response and overall survival in HNC patients treated with chemoradiotherapy. Those with high 53BP1 expression could derive only a meager benefit from treatment. Analysis of BRCA1 and RAP80 could further reinforce the predictive value of 53BP1. Although this was a retrospective study with small sample size, it could inform larger translational studies in HNC.