title: Development of prognostic signatures for intermediate-risk papillary thyroid cancer.
abstract: The incidence of Papillary thyroid carcinoma (PTC), the most common type of thyroid malignancy, has risen rapidly worldwide. PTC usually has an excellent prognosis. However, the rising incidence of PTC, due at least partially to widespread use of neck imaging studies with increased detection of small cancers, has created a clinical issue of overdiagnosis, and consequential overtreatment. We investigated how molecular data can be used to develop a prognostics signature for PTC.
  
  
  
  The Cancer Genome Atlas (TCGA) recently reported on the genomic landscape of a large cohort of PTC cases. In order to decrease unnecessary morbidity associated with over diagnosing PTC patient with good prognosis, we used TCGA data to develop a gene expression signature to distinguish between patients with good and poor prognosis. We selected a set of clinical phenotypes to define an 'extreme poor' prognosis group and an 'extreme good' prognosis group and developed a gene signature that characterized these.
  
  
  
  We discovered a gene expression signature that distinguished the extreme good from extreme poor prognosis patients. Next, we applied this signature to the remaining intermediate risk patients, and show that they can be classified in clinically meaningful risk groups, characterized by established prognostic disease phenotypes. Analysis of the genes in the signature shows many known and novel genes involved in PTC prognosis.
  
  
  
  This work demonstrates that using a selection of clinical phenotypes and treatment variables, it is possible to develop a statistically useful and biologically meaningful gene signature of PTC prognosis, which may be developed as a biomarker to help prevent overdiagnosis.
authors.affiliation: Division of Biomedical Informatics Research, Department of Medicine, Stanford University, 1265 Welch Road, Stanford, CA, 94305-5479, USA.
authors.forename: Kevin
authors.identifier: 0000-0001-9018-9852
authors.initials: K
authors.lastname: Brennan
authors.affiliation: Division of Head and Neck Surgery, Department of Otolaryngology-Head and Neck Surgery, Stanford University, 801 Welch Road, Stanford, CA, 94304-1611, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Holsinger
authors.affiliation: Division of Endocrinology, Department of Medicine, Stanford University, 300 Pasteur Drive, Stanford, CA, 94305-5103, USA.
authors.forename: Chrysoula
authors.initials: C
authors.lastname: Dosiou
authors.affiliation: Division of Head and Neck Surgery, Department of Otolaryngology-Head and Neck Surgery, Stanford University, 801 Welch Road, Stanford, CA, 94304-1611, USA.
authors.forename: John B
authors.initials: JB
authors.lastname: Sunwoo
authors.affiliation: Division of Endocrinology, Department of Medicine, Stanford University, 300 Pasteur Drive, Stanford, CA, 94305-5103, USA.
authors.forename: Haruko
authors.initials: H
authors.lastname: Akatsu
authors.affiliation: Division of Oncology, Department of Medicine, Stanford University, 265 Campus Drive, Stanford, CA, 94305-5458, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Haile
authors.affiliation: Stanford Center for Biomedical Informatics Research, Department of Medicine & Department of Biomedical Data Science, Stanford University, Stanford, USA. olivier.gevaert@stanford.edu.
authors.forename: Olivier
authors.initials: O
authors.lastname: Gevaert
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D002291:Carcinoma, Papillary; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D013950:Thymus Gland / Q000378:metabolism; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor
keywords: Gene expression; Papillary thyroid cancer; Prognosis