Dept. of Oncology-Pathology, Karolinska Institutet, 171 76 Stockholm, Sweden.
Dept. of Surgical and Perioperative Sciences, Umeå University, 901 87 Umeå, Sweden.
Oral Oncol. 2018 Jul;82:8-16. doi: 10.1016/j.oraloncology.2018.04.021. Epub 2018 May 4.
Three-year disease-free survival (DFS) is 80% for human papillomavirus (HPV) positive tonsillar and base of tongue cancer (TSCC/BOTSCC) treated with radiotherapy alone, and today's intensified therapy does not improve prognosis. More markers are therefore needed to more accurately identify patients with good prognosis or in need of alternative therapy. Here, microRNAs (miRs) 155, 185 and 193b were examined as potential prognostic markers in TSCC/BOTSCC.
168 TSCC/BOTSCC patients diagnosed 2000-2013, with known data on HPV-status, CD8 tumour infiltrating lymphocytes, tumour staging and survival were examined for expression of miR-155, -185 and -193b using Real-Time PCR. Associations between miR expression and patient and tumour characteristics were analysed using univariate testing and multivariate regression.
Tumours compared to normal tonsils showed decreased miR-155 and increased miR-193b expression. miR-155 expression was associated with HPV-positivity, low T-stage, high CD8 TIL counts and improved survival. miR-185 expression was associated with HPV-negativity and a tendency towards decreased survival, while miR-193b expression was associated with higher T-stage, male gender and lower CD8 TIL counts, but not with outcome. Upon Cox regression, miR-185 was the only miR significantly associated with survival. Combining miR-155 and miR-185 to predict outcome in HPV patients yielded an area under curve (AUC) of 71%.
Increased miR-155 expression was found as a positive predictor of survival, with the effect mainly due to its association with high CD8 TIL numbers, while miR-185 independently associated with decreased survival. Addition of these miRs to previously validated prognostic biomarkers could improve patient stratification accuracy.
单纯接受放疗的 HPV 阳性扁桃体和舌根癌（TSCC/BOTSCC）患者 3 年无病生存率（DFS）为 80%，而目前的强化治疗并不能改善预后。因此，需要更多的标志物来更准确地识别预后良好或需要替代治疗的患者。在此，研究人员检查了 microRNAs（miRs）155、185 和 193b 是否可作为 TSCC/BOTSCC 的潜在预后标志物。
对 2000 年至 2013 年间诊断为 TSCC/BOTSCC 的 168 例患者进行了检查，这些患者已知 HPV 状态、CD8 肿瘤浸润淋巴细胞、肿瘤分期和生存数据，并使用实时 PCR 检测 miR-155、-185 和 -193b 的表达。使用单变量检验和多变量回归分析 miR 表达与患者和肿瘤特征之间的关系。
与正常扁桃体相比，肿瘤中 miR-155 的表达降低，miR-193b 的表达升高。miR-155 表达与 HPV 阳性、低 T 分期、高 CD8 TIL 计数和改善的生存相关。miR-185 表达与 HPV 阴性和生存趋势降低相关，而 miR-193b 表达与更高的 T 分期、男性和较低的 CD8 TIL 计数相关，但与结局无关。在 Cox 回归中，miR-185 是唯一与生存显著相关的 miR。将 miR-155 和 miR-185 结合起来预测 HPV 患者的预后，曲线下面积（AUC）为 71%。
miR-155 表达增加被发现是生存的正预测因子，其作用主要归因于与高 CD8 TIL 数量的关联，而 miR-185 则独立与生存降低相关。将这些 miRs 添加到以前验证过的预后生物标志物中，可以提高患者分层的准确性。
