Purpose

Progress in radiation therapy of head and neck squamous cell carcinomas (HNSCCs) is logically linked to the development of molecular predictors that would help to enhance individually tailored treatment. MicroRNA (miRNA) expression profiles in tumors have repeatedly been tested to optimize the molecular diagnostics of HNSCC. In addition to tumor tissues, miRNAs are stably present in body fluids, including saliva, and can thus be collected non-invasively. The aim of our current study was to evaluate whether salivary miRNAs have potential as response predictors in HNSCC patients treated with intensity modulated radiation therapy (IMRT).

Methods

In total 48 HNSCC patients treated by definitive IMRT were enrolled in our prospective study. To identify predictive salivary miRNAs, we used small RNA sequencing in 14 saliva samples of HNSCC patients and qRT-PCR validation of selected miRNA candidates in an independent set of 34 patients.

Results

We found that salivary miR-15a-5p and miR-15b-5p exhibited differential levels between patients with and without complete remission (p = 0.025 and p = 0.028, respectively). Subsequent Kaplan-Meier analysis confirmed that patients with higher levels of miR-15a-5p reached a significantly longer locoregional progression-free survival (LPFS) than those with low levels (p = 0.024). Finally, multivariate Cox regression analysis revealed that miR-15a-5p may serve as an independent predictive biomarker of LPFS in HNSCC patients treated with IMRT (HR 0.104; 95% CI 0.004–0.911; p = 0.04).

Conclusions

We conclude that salivary miR-15a-5p may represent a potential biomarker for individualized treatment decision-making in HNSCC patients.

中文翻译：

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通过小RNA测序鉴定的唾液微RNA可作为头颈癌患者对强度调节放疗反应的潜在预测指标。

目的

头颈鳞状细胞癌（HNSCC）放射治疗的进展与分子预测因子的发展在逻辑上联系在一起，分子预测因子的发展将有助于增强个性化治疗。反复测试了肿瘤中的MicroRNA（miRNA）表达谱，以优化HNSCC的分子诊断。除肿瘤组织外，miRNA稳定存在于体液（包括唾液）中，因此可以无创收集。我们当前研究的目的是评估唾液中的miRNA是否具有潜力，作为接受强度调制放射治疗（IMRT）的HNSCC患者的反应预测因子。

方法

通过前瞻性IMRT治疗的总共48例HNSCC患者参加了我们的前瞻性研究。为了鉴定预测性唾液miRNA，我们对14例HNSCC患者的唾液样本进行了小RNA测序，并对34例患者中的一组独立的miRNA候选者进行了qRT-PCR验证。

结果

我们发现，唾液中的miR-15a-5p和miR-15b-5p在有和没有完全缓解的患者之间表现出差异水平（分别为p  = 0.025和p  = 0.028）。随后的Kaplan-Meier分析证实，与低水平的患者相比，高水平的miR-15a-5p患者的局部无进展生存期（LPFS）明显更长（p  = 0.024）。最后，多因素Cox回归分析显示，miR-15a-5p可以作为IMRT治疗的HNSCC患者LPFS的独立预测生物标志物（HR 0.104； 95％CI 0.004-0.911；p  = 0.04）。

结论

我们得出的结论是，唾液中miR-15a-5p可能代表HNSCC患者个体化治疗决策的潜在生物标志物。