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Clin Cancer Res. 2019 Mar 15;25(6):1795-1808. doi: 10.1158/1078-0432.CCR-18-1884. Epub 2018 Dec 20.

Molecular Classification of Lymph Node Metastases Subtypes Predict for Survival in Head and Neck Cancer.

Author information

1
Center for Research Informatics, University of Chicago, Chicago, Illinois.
2
Department of Pathology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois.
3
Department of Radiation and Cellular Oncology, University of Chicago Medical Center, Chicago, Illinois.
4
Department of Otolaryngology-Head and Neck Surgery, University of Illinois Hospital and Health Sciences System, Chicago, Illinois.
5
Department of Medicine, University of Illinois Hospital and Health Sciences System, Chicago, Illinois.
6
Department of Radiation Oncology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois.
7
Ludwig Center for Metastasis Research, The University of Chicago, Chicago, Illinois.
8
Department of Radiation and Cellular Oncology, University of Chicago Medical Center, Chicago, Illinois. mspiotto@radonc.uchicago.edu.
#
Contributed equally

Abstract

PURPOSE:

In advanced stage head and neck squamous cell cancers (HNSCC), approximately half of the patients with lymph node metastases (LNM) are not cured. Given the heterogeneous outcomes in these patients, we profiled the expression patterns of LNMs to identify the biological factors associated with patient outcomes.Experimental Design: We performed mRNAseq and miRNAseq on 72 LNMs and 29 matched primary tumors from 34 patients with HNSCC. Clustering identified molecular subtypes in LNMs and in primary tumors. Prediction Analysis of Microarrays algorithm identified a 73-gene classifier that distinguished LNM subtypes. Gene-set enrichment analysis identified pathways upregulated in LNM subtypes.

RESULTS:

Integrative clustering identified three distinct LNM subtypes: (i) an immune subtype (Group 1), (ii) an invasive subtype (Group 2), and (iii) a metabolic/proliferative subtype (Group 3). Group 2 subtype was associated with significantly worse locoregional control and survival. LNM-specific subtypes were not observed in matched primary tumor specimens. In HNSCCs, breast cancers, and melanomas, a 73-gene classifier identified similar Group 2 LNM subtypes that were associated with worse disease control and survival only when applied to lymph node sites, but not when applied to other primary tumors or metastatic sites. Similarly, previously proposed prognostic classifiers better distinguished patients with worse outcomes when applied to the transcriptional profiles of LNMs, but not the profiles of primary tumors.

CONCLUSIONS:

The transcriptional profiles of LNMs better predict outcomes than transcriptional profiles of primary tumors. The LNMs display site-specific subtypes associated with worse disease control and survival across multiple cancer types.

PMID:
30573692
PMCID:
PMC6420850
[Available on 2020-03-15]
DOI:
10.1158/1078-0432.CCR-18-1884

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