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Cancers (Basel). 2018 Dec 5;10(12). pii: E494. doi: 10.3390/cancers10120494.

Immune Gene Signature Delineates a Subclass of Papillary Thyroid Cancer with Unfavorable Clinical Outcomes.

Kim K1,2,3, Jeon S4,5, Kim TM6,7,8, Jung CK9,10,11.

Author information

1
Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. kyuryung.kim@catholic.ac.kr.
2
Department of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. kyuryung.kim@catholic.ac.kr.
3
Department of Biomedicine & Health Sciences, Graduate School, The Catholic University of Korea, Seoul 06591, Korea. kyuryung.kim@catholic.ac.kr.
4
Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. thfk38@nate.com.
5
Department of Biomedicine & Health Sciences, Graduate School, The Catholic University of Korea, Seoul 06591, Korea. thfk38@nate.com.
6
Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. tmkim@catholic.ac.kr.
7
Department of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. tmkim@catholic.ac.kr.
8
Department of Biomedicine & Health Sciences, Graduate School, The Catholic University of Korea, Seoul 06591, Korea. tmkim@catholic.ac.kr.
9
Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. ckjung@catholic.ac.kr.
10
Department of Biomedicine & Health Sciences, Graduate School, The Catholic University of Korea, Seoul 06591, Korea. ckjung@catholic.ac.kr.
11
Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. ckjung@catholic.ac.kr.

Abstract

Papillary thyroid carcinoma (PTC) represents a heterogeneous disease with diverse clinical outcomes highlighting a need to identify robust biomarkers with clinical relevance. We applied non-negative matrix factorization-based deconvolution to publicly available gene expression profiles of thyroid cancers in the Cancer Genome Atlas (TCGA) consortium. Among three metagene signatures identified, two signatures were enriched in canonical BRAF-like and RAS-like thyroid cancers with up-regulation of genes involved in oxidative phosphorylation and cell adhesions, respectively. The third metagene signature representing up-regulation of immune-related genes further segregated BRAF-like and RAS-like PTCs into their respective subgroups of immunoreactive (IR) and immunodeficient (ID), respectively. BRAF-IR PTCs showed enrichment of tumor infiltrating immune cells, tall cell variant PTC, and shorter recurrence-free survival compared to BRAF-ID PTCs. RAS-IR and RAS-ID PTC subtypes included majority of normal thyroid tissues and follicular variant PTC, respectively. Immunopathological features of PTC subtypes such as immune cell fraction, repertoire of T cell receptors, cytolytic activity, and expression level of immune checkpoints such as and PD-L1 and CTLA-4 were consistently observed in two different cohorts. Taken together, an immune-related metagene signature can classify PTCs into four molecular subtypes, featuring the distinct histologic type, genetic and transcriptional alterations, and potential clinical significance.

KEYWORDS:

immunity; molecular taxonomy; non-negative matrix factorization; papillary thyroid carcinoma; survival

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