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The role of HPV RNA transcription, immune response‐related gene expression and disruptive TP53 mutations in diagnostic and prognostic profiling of head and neck cancer
Author(s) -
Wichmann Gunnar,
Rosolowski Maciej,
Krohn Knut,
Kreuz Markus,
Boehm Andreas,
Reiche Anett,
Scharrer Ulrike,
Halama Dirk,
Bertolini Julia,
Bauer Ulrike,
Holzinger Dana,
Pawlita Michael,
Hess Jochen,
Engel Christoph,
Hasenclever Dirk,
Scholz Markus,
Ahnert Peter,
Kirsten Holger,
Hemprich Alexander,
Wittekind Christian,
Herbarth Olf,
Horn Friedemann,
Dietz Andreas,
Loeffler Markus
Publication year - 2015
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.29649
Subject(s) - gene , gene expression , rna , cancer research , biology , head and neck squamous cell carcinoma , gene expression profiling , metastasis , lymph node , head and neck cancer , cancer , immunology , genetics
Stratification of head and neck squamous cell carcinomas (HNSCC) based on HPV16 DNA and RNA status, gene expression patterns, and mutated candidate genes may facilitate patient treatment decision. We characterize head and neck squamous cell carcinomas (HNSCC) with different HPV16 DNA and RNA (E6*I) status from 290 consecutively recruited patients by gene expression profiling and targeted sequencing of 50 genes. We show that tumors with transcriptionally inactive HPV16 (DNA+ RNA‐) are similar to HPV‐negative (DNA‐) tumors regarding gene expression and frequency of TP53 mutations (47%, 8/17 and 43%, 72/167, respectively). We also find that an immune response‐related gene expression cluster is associated with lymph node metastasis, independent of HPV16 status and that disruptive TP53 mutations are associated with lymph node metastasis in HPV16 DNA‐ tumors. We validate each of these associations in another large data set. Four gene expression clusters which we identify differ moderately but significantly in overall survival. Our findings underscore the importance of measuring the HPV16 RNA (E6*I) and TP53 ‐mutation status for patient stratification and identify associations of an immune response‐related gene expression cluster and TP53 mutations with lymph node metastasis in HNSCC.