Hess Anne-Katrin, Müer Annika, Mairinger Fabian Dominik, Weichert Wilko, Stenzinger Albrecht, Hummel Michael, Budach Volker, Tinhofer Ingeborg
Translational Radiooncology Research Laboratory, Department of Radiooncology and Radiotherapy, Charité University Hospital, Berlin, Germany.
Institute of Pathology, Charité University Hospital, Berlin, Germany.
Eur J Cancer. 2017 May;77:3-12. doi: 10.1016/j.ejca.2017.02.018. Epub 2017 Mar 26.
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.
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 nanoString 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.
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.
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.
评估了肿瘤细胞和浸润免疫细胞中的微小RNA（miRNA）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。
从在ARO-0401 III期试验中接受放疗联合5-氟尿嘧啶/顺铂（CDDP-CRTX）或5-氟尿嘧啶/丝裂霉素C（MMC-CRTX）治疗的局部晚期HNSCC患者中收集福尔马林固定、石蜡包埋的肿瘤材料。分别通过Affymetrix miRNA微阵列和nanoString泛癌免疫分析在48例口咽癌（OPSCC）病例的测试队列中建立miRNA和免疫图谱。通过实时PCR在149例HNSCC患者中检测候选miRNA的表达。通过Kaplan-Meier和Cox回归分析确定miRNA图谱对CRTX疗效的干扰。
5种miRNA（miR-27b、-130b、-200b、-451和-532-5p）的表达水平与MMC-CRTX后的总生存期显著相关。6种不同的miRNA（miR-125b、-146a、-150、-155、-187和-342-5p）与CDDP-CRTX后的总生存期相关。实时PCR验证证实了miR-200b和miR-155在OPSCC中的预测价值，而在下咽癌中不存在。miR-146a被揭示为两种CRTX方案的预后标志物。miR-200b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-146a被确定为肿瘤浸润淋巴细胞的替代标志物。
miR-200b和miR-155被确立为CRTX两种标准方案个性化治疗选择的潜在标志物。miR-155的预测作用值得进一步研究，尤其是在CRTX/免疫检查点抑制剂联合临床试验的框架内。
