Journal Article

DKFZ-2019-00779

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A Five-MicroRNA Signature Predicts Survival and Disease Control of Patients with Head and Neck Cancer Negative for HPV Infection.

Hess, J. ; Unger, K. ; Maihoefer, C. ; Schüttrumpf, L. ; Wintergerst, L. ; Heider, T. ; Weber, P. ; Marschner, S. ; Braselmann, H. ; Samaga, D. ; Kuger, S. ; Pflugradt, U. ; Baumeister, P. ; Walch, A. ; Woischke, C. ; Kirchner, T.DKFZ* ; Werner, M.DKFZ* ; Werner, K.DKFZ* ; Baumann, M.DKFZ* ; Budach, V.DKFZ* ; Combs, S. E.DKFZ* ; Debus, J.DKFZ* ; Grosu, A.-L.DKFZ* ; Krause, M.DKFZ* ; Linge, A. ; Rödel, C.DKFZ* ; Stuschke, M.DKFZ* ; Zips, D.DKFZ* ; Zitzelsberger, H. ; Ganswindt, U. ; Henke, M.DKFZ* ; Belka, C.DKFZ*

2019
AACR Philadelphia, Pa. [u.a.]

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Please use a persistent id in citations: doi:10.1158/1078-0432.CCR-18-0776

Abstract: Human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is associated with unfavorable prognosis, while independent prognostic markers remain to be defined.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; n = 85). Selection fulfilled comparable demographic, treatment, and follow-up characteristics. Findings were validated in an independent single-center patient sample (LMU-KKG; n = 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.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, P < 0.001], which was confirmed in LMU-KKG (HR 4.24; 95% CI, 1.40-12.81, P = 0.005). The signature also predicted overall survival (HR 3.03; 95% CI, 1.50-6.12, P = 0.001), recurrence-free survival (HR 3.16; 95% CI, 1.65-6.04, P < 0.001), and disease-specific survival (HR 5.12; 95% CI, 1.88-13.92, P < 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 (n = 17), low-intermediate (n = 80), high-intermediate (n = 48), or high risk (n = 17) for recurrence (P < 0.001).The five-miRNA signature is a strong and independent prognostic factor for disease recurrence and survival of patients with HPV-negative HNSCC.See related commentary by Clump et al., p. 1441.

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Contributing Institute(s):

1. E220 Radioonkologie Radiobiologie (E220)
2. DKTK Dresden (L301)
3. DKTK Freiburg (L601)
4. DKTK München (L701)
5. DKTK Frankfurt (L501)
6. DKTK Essen (L401)
7. DKTK Tübingen (L801)
8. DKTK Berlin (L201)
9. DKTK Heidelberg (L101)
10. E050 KKE Strahlentherapie (E050)

Research Program(s):

1. 315 - Imaging and radiooncology (POF3-315) (POF3-315)

Appears in the scientific report 2019

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; IF >= 10 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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