MiR-200b and miR-155 as predictive biomarkers for the efficacy of chemoradiation in locally advanced head and neck squamous cell carcinoma
MiR-200b and miR-155 as predictive biomarkers for the efficacy of chemoradiation in locally advanced head and neck squamous cell carcinoma
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DOI：
10.1016/j.ejca.2017.02.018
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发表时间：
2017-05-01
影响因子：
8.4
通讯作者：
Tinhofer, Ingeborg
中科院分区：
文献类型：
--
作者：
Hess, Anne-Katrin;Mueer, Annika;Tinhofer, Ingeborg
背景资料：评估肿瘤细胞和浸润免疫细胞中microRNAs（miRNAs）对局部晚期头颈部鳞状细胞癌（HNSCC）放化疗（CRTX）疗效的预测价值。福尔马林固定，从ARO-0401 III期试验中接受放疗联合5-氟尿嘧啶/顺铂治疗的局部晚期HNSCC患者中收集石蜡包埋的肿瘤材料（CDDP-CRTX）或5-氟尿嘧啶/丝裂霉素C（MMC-CRTX）。在48例口咽癌（OPSCC）病例的测试队列中，分别通过AffymiRNA微阵列和nano-String PanCancer Immune Panel建立了miRNA和免疫谱。通过实时PCR测量149例HNSCC患者中miRNA候选物的表达。结果：5种miRNA（miR-27 b、-130b、-200b、-451和-532-5p）的表达水平与MMC-CRTX后的总生存率显著相关。6种不同的miRNA（miR-125 b、-146a、-150、-155、-187和-342-5p）与CDDP-CRTX后的总生存率相关。通过实时PCR验证证实了miR-200 b和miR-155在OPSCC中的预测价值，这在下咽癌中不存在。miR-146 a被揭示为两种CRTX方案的预后标志物。miR-200 b的表达主要与远处转移相关，而miR-155与局部复发相关。miR-155和miR-146 a被确定为肿瘤浸润淋巴细胞的替代标记物。结论：miR-200 b和miR-155被确定为CRTX的两种标准方案的个体化治疗选择的潜在标记物。miR-155的预测作用值得进一步研究，特别是在CRTX/免疫检查点抑制剂组合的临床试验框架内。(c)2017爱思唯尔有限公司版权所有
Background: The predictive value of microRNAs (miRNAs) in tumour cells and infiltrating immune cells for the efficacy of chemoradiation (CRTX) in locally advanced head and neck squamous cell carcinoma (HNSCC) was evaluated.Methods: Formalin-fixed, paraffin-embedded tumour material was collected from patients with locally advanced HNSCC treated within the ARO-0401 phase III trial with radiotherapy in combination with either 5-fluorouracil/cisplatin (CDDP-CRTX) or 5-fluorouracil/mitomycin C (MMC-CRTX). MiRNA and immune profiles were established in a test cohort of 48 oropharyngeal carcinoma (OPSCC) cases by Affymetrix miRNA microarrays and the nano-String PanCancer Immune Panel, respectively. Expression of miRNA candidates was measured in 149 HNSCC patients by real-time PCR. Interference of miRNA profiles with CRTX efficacy was determined by Kaplan-Meier and Cox regression analysis.Results: Expression levels of five miRNAs (miR-27b, -130b, -200b, -451 and -532-5p) were significantly associated with overall survival after MMC-CRTX. Six different miRNAs (miR-125b, -146a, -150, -155, -187 and -342-5p) were correlated with overall survival after CDDP-CRTX. Validation by real-time PCR confirmed the predictive value of miR-200b and miR-155 in OPSCC, which was absent in hypopharyngeal carcinomas. MiR-146a was revealed as a prognostic marker for both CRTX regimens. MiR-200b expression was mainly associated with distant metastasis, whereas miR-155 correlated with local recurrence. MiR-155 and miR-146a were identified as surrogate markers for tumour-infiltrating lymphocytes.Conclusions: MiR-200b and miR-155 were established as potential markers for personalised treatment selection of two standard regimens of CRTX. The predictive role of miR-155 deserves further investigation, especially within the framework of clinical trials of CRTX/immune checkpoint inhibitor combinations. (c) 2017 Elsevier Ltd. All rights reserved.