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BMC Cancer. 2018 Jan 10;18(1):68. doi: 10.1186/s12885-017-3948-3.

CRABP1, C1QL1 and LCN2 are biomarkers of differentiated thyroid carcinoma, and predict extrathyroidal extension.

Celestino R1,2,3,4, Nome T3,5, Pestana A1,2,6, Hoff AM3,5, Gonçalves AP1,6,7, Pereira L1,2, Cavadas B1,2, Eloy C1,2, Bjøro T8,9, Sobrinho-Simões M1,2,10,11, Skotheim RI12,13, Soares P14,15,16.

Author information

1
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal.
2
IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal.
3
Department of Molecular Oncology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, P.O.Box 4953 Nydalen, 0424, Oslo, Norway.
4
School of Allied Health Technologies, Polytechnic of Porto, Rua Dr. António Bernardino de Almeida, 400, 4200-072, Porto, Portugal.
5
Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, 0424, Oslo, Norway.
6
ICBAS - Abel Salazar Biomedical Sciences Institute of the University of Porto, 4050-313, Porto, Portugal.
7
IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal.
8
Department of Medical Biochemistry, Norwegian Radium Hospital, Oslo University Hospital, 0424, Oslo, Norway.
9
Institute of Clinical Medicine, University of Oslo, 0318, Oslo, Norway.
10
Department of Pathology, Medical Faculty, University of Porto, 4200-319, Porto, Portugal.
11
Department of Pathology, Centro Hospitalar de São João, 4200-319, Porto, Portugal.
12
Department of Molecular Oncology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, P.O.Box 4953 Nydalen, 0424, Oslo, Norway. Rolf.I.Skotheim@rr-research.no.
13
Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, 0424, Oslo, Norway. Rolf.I.Skotheim@rr-research.no.
14
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal. psoares@ipatimup.pt.
15
IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal. psoares@ipatimup.pt.
16
Department of Pathology, Medical Faculty, University of Porto, 4200-319, Porto, Portugal. psoares@ipatimup.pt.

Abstract

BACKGROUND:

The prognostic variability of thyroid carcinomas has led to the search for accurate biomarkers at the molecular level. Follicular thyroid carcinoma (FTC) is a typical example of differentiated thyroid carcinomas (DTC) in which challenges are faced in the differential diagnosis.

METHODS:

We used high-throughput paired-end RNA sequencing technology to study four cases of FTC with different degree of capsular invasion: two minimally invasive (mFTC) and two widely invasive FTC (wFTC). We searched by genes differentially expressed between mFTC and wFTC, in an attempt to find biomarkers of thyroid cancer diagnosis and/or progression. Selected biomarkers were validated by real-time quantitative PCR in 137 frozen thyroid samples and in an independent dataset (TCGA), evaluating the diagnostic and the prognostic performance of the candidate biomarkers.

RESULTS:

We identified 17 genes significantly differentially expressed between mFTC and wFTC. C1QL1, LCN2, CRABP1 and CILP were differentially expressed in DTC in comparison with normal thyroid tissues. LCN2 and CRABP1 were also differentially expressed in DTC when compared with follicular thyroid adenoma. Additionally, overexpression of LCN2 and C1QL1 were found to be independent predictors of extrathyroidal extension in DTC.

CONCLUSIONS:

We conclude that the underexpression of CRABP1 and the overexpression of LCN2 may be useful diagnostic biomarkers in thyroid tumours with questionable malignity, and the overexpression of LCN2 and C1QL1 may be useful for prognostic purposes.

KEYWORDS:

Biomarker; C1QL1; CILP; CRABP1; Cancer; Gene expression; LCN2; RNA sequencing; TCGA; Thyroid

PMID:
29321030
PMCID:
PMC5763897
DOI:
10.1186/s12885-017-3948-3
[Indexed for MEDLINE]
Free PMC Article

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