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

被引：54

作者：

Hess, Julia ^{[1
,2
]}

Unger, Kristian ^{[1
,2
]}

Maihoefer, Cornelius ^{[2
,3
]}

Schuettrumpf, Lars ^{[2
,3
]}

Wintergerst, Ludmila ^{[1
,2
]}

Heider, Theresa ^{[1
,2
]}

Weber, Peter ^{[1
,2
,4
,5
]}

Marschner, Sebastian ^{[2
,3
]}

Braselmann, Herbert ^{[1
,2
]}

Samaga, Daniel ^{[1
,2
]}

Kuger, Sebastian ^{[1
]}

Pflugradt, Ulrike ^{[2
,3
]}

Baumeister, Philipp ^{[2
,6
]}

Walch, Axel ^{[7
]}

Woischke, Christine ^{[8
]}

Kirchner, Thomas ^{[8
,9
,10
]}

Werner, Martin ^{[10
,11
,12
,13
]}

Werner, Kristin ^{[10
,11
,12
,13
]}

Baumann, Michael ^{[10
,14
]}

Budach, Volker ^{[10
,15
,16
]}

Combs, Stephanie E. ^{[9
,10
,17
,18
]}

Debus, Juergen ^{[10
,19
,20
]}

Grosu, Anca-Ligia ^{[10
,13
,21
]}

Krause, Mechthild ^{[10
,14
,22
,23
,24
,25
]}

Linge, Annett ^{[10
,14
,22
,23
,24
,25
,26
]}

Roedel, Claus ^{[10
,27
,28
]}

Stuschke, Martin ^{[10
,29
,30
]}

Zips, Daniel ^{[10
,31
,32
,33
]}

Zitzelsberger, Horst ^{[1
,2
,3
]}

Ganswindt, Ute ^{[2
,3
,34
]}

Henke, Michael ^{[10
,21
]}

Belka, Claus ^{[2
,3
,9
,10
]}

机构：

[1] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Res Unit Radiat Cytogenet, Neuherberg, Germany

[2] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Clin Cooperat Grp Personalized Radiotherapy Head, Neuherberg, Germany

[3] Ludwig Maximilians Univ Munchen, Univ Hosp, Dept Radiat Oncol, Munich, Germany

[4] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, IDC, Neuherberg, Germany

[5] Heidelberg Univ Hosp, Joint Heidelberg IDC Translat Diabet Program, Heidelberg, Germany

[6] Ludwig Maximilians Univ Munchen, Dept Otorhinolaryngol Head & Neck Surg, Univ Hosp, Munich, Germany

[7] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Res Unit Analyt Pathol, Neuherberg, Germany

[8] Ludwig Maximilians Univ Munchen, Fac Med, Inst Pathol, Munich, Germany

[9] German Canc Consortium DKTK, Partner Site Munich, Heidelberg, Germany

[10] German Canc Res Ctr, Heidelberg, Germany

[11] Univ Freiburg, Med Ctr, Inst Surg Pathol, Freiburg, Germany

[12] Univ Freiburg, Fac Med, Freiburg, Germany

[13] German Canc Consortium DKTK, Partner Site Freiburg, Heidelberg, Germany

[14] German Canc Consortium DKTK, Partner Site Dresden, Heidelberg, Germany

[15] Charite, Dept Radiooncol & Radiotherapy, Berlin, Germany

[16] German Canc Consortium DKTK, Partner Site Berlin, Heidelberg, Germany

[17] Tech Univ Munich, Klinikum Rechts Isar, Dept Radiat Oncol, Munich, Germany

[18] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Inst Innovat Radiotherapy iRT, Neuherberg, Germany

[19] Heidelberg Univ, Heidelberg Ion Therapy Ctr HIT, Dept Radiat Oncol, Heidelberg, Germany

[20] German Canc Consortium DKTK, Partner Site Heidelberg, Heidelberg, Germany

[21] Univ Freiburg, Fac Med, Med Ctr, Dept Radiat Oncol, Freiburg, Germany

[22] Tech Univ Dresden, Fac Med, Dept Radiotherapy & Radiat Oncol, Dresden, Germany

[23] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dresden, Germany

[24] Tech Univ Dresden, Fac Med, OncoRay Natl Ctr Radiat Res Oncol, Dresden, Germany

[25] Natl Ctr Tumor Dis NCT, Partner Site Dresden, Dresden, Germany

[26] Helmholtz Zentrum Dresden Rossendorf, Inst Radiooncol OncoRay Dresden, Dresden, Germany

[27] Goethe Univ Frankfurt, Dept Radiotherapy & Oncol, Frankfurt, Germany

[28] German Canc Consortium DKTK, Partner Site Frankfurt, Heidelberg, Germany

[29] Univ Duisburg Essen, Fac Med, Dept Radiotherapy, Essen, Germany

[30] German Canc Consortium DKTK, Partner Site Essen, Heidelberg, Germany

[31] Eberhard Karls Univ Tubingen, Fac Med, Dept Radiat Oncol, Tubingen, Germany

[32] Eberhard Karls Univ Tubingen, Univ Hosp Tubingen, Tubingen, Germany

[33] German Canc Consortium DKTK, Partner Site Tubingen, Heidelberg, Germany

[34] Innsbruck Med Univ, Dept Therapeut Radiol & Oncol, Innsbruck, Austria

来源：

CLINICAL CANCER RESEARCH | 2019年 / 25卷 / 05期

关键词：

SQUAMOUS-CELL CARCINOMA; MICRORNA EXPRESSION; OROPHARYNGEAL CANCER; PROGNOSTIC-FACTOR; PROGRESSION; VALIDATION; HYPOXIA; RISK; IDENTIFICATION; HSA-MIR-210;

D O I：

10.1158/1078-0432.CCR-18-0776

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose: Human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is associated with unfavorable prognosis, while independent prognostic markers remain to be defined. Experimental Design: 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. Recursivepartitioning 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. Results: 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, hsamiR- 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). Conclusions: The five-miRNA signature is a strong and independent prognostic factor for disease recurrence and survival of patients with HPV-negative HNSCC.

引用

页码：1505 / 1516

页数：12

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