Immune Gene Signature Delineates a Subclass of Papillary Thyroid Cancer with Unfavorable Clinical Outcomes
1
Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
2
Department of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
3
Department of Biomedicine & Health Sciences, Graduate School, The Catholic University of Korea, Seoul 06591, Korea
4
Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
*
Authors to whom correspondence should be addressed.
Cancers 2018, 10(12), 494; https://doi.org/10.3390/cancers10120494
Received: 17 November 2018
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Revised: 2 December 2018
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Accepted: 3 December 2018
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Published: 5 December 2018
(This article belongs to the Special Issue Thyroid Cancer)
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.
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Keywords:
papillary thyroid carcinoma; immunity; molecular taxonomy; non-negative matrix factorization; survival
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Description: The following are available online at www.mdpi.com/xxx/s1, Table S1: GSEA of three metagene signatures. Top 20 Gene Ontology terms significantly enriched with gene-level weights of 3 metagene signatures are shown. ES and NES are enrichment score and normalized ES as the output of GSEA, respectively, Table S2: Gene-level weights and metagene factors for GSEA of 3 metagene signatures. For 3 metagene signatures, weights for GSEA and metagene factors for metagene projection are shown. The genes in each metagene signature are sorted in order of the weight values, Table S3: Sequencing information of RNAseq (CMC cohort).
MDPI and ACS Style
Kim, K.; Jeon, S.; Kim, T.-M.; Jung, C.K. Immune Gene Signature Delineates a Subclass of Papillary Thyroid Cancer with Unfavorable Clinical Outcomes. Cancers 2018, 10, 494. https://doi.org/10.3390/cancers10120494
AMA Style
Kim K, Jeon S, Kim T-M, Jung CK. Immune Gene Signature Delineates a Subclass of Papillary Thyroid Cancer with Unfavorable Clinical Outcomes. Cancers. 2018; 10(12):494. https://doi.org/10.3390/cancers10120494
Chicago/Turabian StyleKim, Kyuryung, Sora Jeon, Tae-Min Kim, and Chan K. Jung. 2018. "Immune Gene Signature Delineates a Subclass of Papillary Thyroid Cancer with Unfavorable Clinical Outcomes" Cancers 10, no. 12: 494. https://doi.org/10.3390/cancers10120494
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