Development and Validation of a Gene Signature for Patients with Head and Neck Carcinomas Treated by Postoperative Radio(chemo)therapy

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • DKTK-ROG - (Author)

Abstract

Purpose: The aim of this study was to identify and independently validate a novel gene signature predicting locoregional tumor control (LRC) for treatment individualization of patients with locally advanced HPV-negative head and neck squamous cell carcinomas (HNSCC) who are treated with postoperative radio(chemo)therapy (PORT-C).Experimental Design: Gene expression analyses were performed using NanoString technology on a multicenter training cohort of 130 patients and an independent validation cohort of 121 patients. The analyzed gene set was composed of genes with a previously reported association with radio(chemo)sensitivity or resistance to radio(chemo)therapy. Gene selection and model building were performed comparing several machine-learning algorithms.Results: We identified a 7-gene signature consisting of the three individual genes HILPDA, CD24, TCF3, and one metagene combining the highly correlated genes SERPINE1, INHBA, P4HA2, and ACTN1 The 7-gene signature was used, in combination with clinical parameters, to fit a multivariable Cox model to the training data (concordance index, ci = 0.82), which was successfully validated (ci = 0.71). The signature showed improved performance compared with clinical parameters alone (ci = 0.66) and with a previously published model including hypoxia-associated genes and cancer stem cell markers (ci = 0.65). It was used to stratify patients into groups with low and high risk of recurrence, leading to significant differences in LRC in training and validation (P < 0.001).Conclusions: We have identified and validated the first hypothesis-based gene signature for HPV-negative HNSCC treated by PORT-C including genes related to several radiobiological aspects. A prospective validation is planned in an ongoing prospective clinical trial before potential application in clinical trials for patient stratification. Clin Cancer Res; 24(6); 1364-74. ©2018 AACR.

Details

Original languageEnglish
Pages (from-to)1364-1374
Number of pages11
JournalClinical Cancer Research
Volume24
Issue number6
Publication statusPublished - 15 Mar 2018
Peer-reviewedYes

External IDs

Scopus 85048083415
ORCID /0000-0002-7017-3738/work/142254004

Keywords

Sustainable Development Goals

Keywords

  • Adolescent, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor, Chemoradiotherapy, Child, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Head and Neck Neoplasms/diagnosis, Humans, Male, Middle Aged, Neoplasm Grading, Neoplasm Metastasis, Neoplasm Staging, Postoperative Care, Retrospective Studies, Transcriptome, Treatment Outcome, Young Adult