Data from A Five-MicroRNA Signature Predicts Survival and Disease Control of Patients with Head and Neck Cancer Negative for HPV Infection

Abstract

<div>AbstractPurpose:<p>Human papillomavirus (HPV)–negative head and neck squamous cell carcinoma (HNSCC) is associated with unfavorable prognosis, while independent prognostic markers remain to be defined.</p>Experimental Design:<p>We retrospectively performed miRNA expression profiling. Patients were operated for locally advanced HPV-negative HNSCC and had received radiochemotherapy in eight different hospitals (DKTK-ROG; <i>n</i> = 85). Selection fulfilled comparable demographic, treatment, and follow-up characteristics. Findings were validated in an independent single-center patient sample (LMU-KKG; <i>n</i> = 77). A prognostic miRNA signature was developed for freedom from recurrence and tested for other endpoints. Recursive-partitioning analysis was performed on the miRNA signature, tumor and nodal stage, and extracapsular nodal spread. Technical validation used qRT-PCR. An miRNA–mRNA target network was generated and analyzed.</p>Results:<p>For DKTK-ROG and LMU-KKG patients, the median follow-up was 5.1 and 5.3 years, and the 5-year freedom from recurrence rate was 63.5% and 75.3%, respectively. A five-miRNA signature (hsa-let-7g-3p, hsa-miR-6508-5p, hsa-miR-210-5p, hsa-miR-4306, and hsa-miR-7161-3p) predicted freedom from recurrence in DKTK-ROG [hazard ratio (HR) 4.42; 95% confidence interval (CI), 1.98−9.88, <i>P</i> < 0.001], which was confirmed in LMU-KKG (HR 4.24; 95% CI, 1.40−12.81, <i>P</i> = 0.005). The signature also predicted overall survival (HR 3.03; 95% CI, 1.50−6.12, <i>P</i> = 0.001), recurrence-free survival (HR 3.16; 95% CI, 1.65−6.04, <i>P</i> < 0.001), and disease-specific survival (HR 5.12; 95% CI, 1.88−13.92, <i>P</i> < 0.001), all confirmed in LMU-KKG data. Adjustment for relevant covariates maintained the miRNA signature predicting all endpoints. Recursive-partitioning analysis of both samples combined classified patients into low (<i>n</i> = 17), low-intermediate (<i>n</i> = 80), high-intermediate (<i>n</i> = 48), or high risk (<i>n</i> = 17) for recurrence (<i>P</i> < 0.001).</p>Conclusions:<p>The five-miRNA signature is a strong and independent prognostic factor for disease recurrence and survival of patients with HPV-negative HNSCC.</p><p><i>See related commentary by Clump et al., p. 1441</i></p></div>