Alpha1-Antitrypsin Expression in Human Thyroid Papillary Carcinoma

Poblete, María Teresa; Nualart, Francisco; Pozo, María del; Pérez, Julia; Figueroa, Carlos D.

doi:10.1097/00000478-199608000-00004

Cited by 24 publications

(17 citation statements)

References 28 publications

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“…SERPINA1 has been reported before as a potential diagnostic marker for papillary thyroid carcinoma in a study investigating its protein expression in thyroid biopsy tissue by Immunocytochemistry and Western Blot [19]. In line with our results, they found SERPINA1 immunoreactivity in nine of ten papillary biopsies while the surrounding tissue showed no such reaction.…”

Section: Discussionsupporting

confidence: 92%

Identification of SERPINA1 as single marker for papillary thyroid carcinoma through microarray meta analysis and quantification of its discriminatory power in independent validation

et al. 2011

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BackgroundSeveral DNA microarray based expression signatures for the different clinically relevant thyroid tumor entities have been described over the past few years. However, reproducibility of these signatures is generally low, mainly due to study biases, small sample sizes and the highly multivariate nature of microarrays. While there are new technologies available for a more accurate high throughput expression analysis, we show that there is still a lot of information to be gained from data deposited in public microarray databases. In this study we were aiming (1) to identify potential markers for papillary thyroid carcinomas through meta analysis of public microarray data and (2) to confirm these markers in an independent dataset using an independent technology.MethodsWe adopted a meta analysis approach for four publicly available microarray datasets on papillary thyroid carcinoma (PTC) nodules versus nodular goitre (NG) from N2-frozen tissue. The methodology included merging of datasets, bias removal using distance weighted discrimination (DWD), feature selection/inference statistics, classification/crossvalidation and gene set enrichment analysis (GSEA). External Validation was performed on an independent dataset using an independent technology, quantitative RT-PCR (RT-qPCR) in our laboratory.ResultsFrom meta analysis we identified one gene (SERPINA1) which identifies papillary thyroid carcinoma against benign nodules with 99% accuracy (n = 99, sensitivity = 0.98, specificity = 1, PPV = 1, NPV = 0.98). In the independent validation data, which included not only PTC and NG, but all major histological thyroid entities plus a few variants, SERPINA1 was again markedly up regulated (36-fold, p = 1:3*10-10) in PTC and identification of papillary carcinoma was possible with 93% accuracy (n = 82, sensitivity = 1, specificity = 0.90, PPV = 0.76, NPV = 1). We also show that the extracellular matrix pathway is strongly activated in the meta analysis data, suggesting an important role of tumor-stroma interaction in the carcinogenesis of papillary thyroid carcinoma.ConclusionsWe show that valuable new information can be gained from meta analysis of existing microarray data deposited in public repositories. While single microarray studies rarely exhibit a sample number which allows robust feature selection, this can be achieved by combining published data using DWD. This approach is not only efficient, but also very cost-effective. Independent validation shows the validity of the results from this meta analysis and confirms SERPINA1 as a potent mRNA marker for PTC in a total (meta analysis plus validation) of 181 samples.

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Section: Discussionsupporting

confidence: 92%

Identification of SERPINA1 as single marker for papillary thyroid carcinoma through microarray meta analysis and quantification of its discriminatory power in independent validation

et al. 2011

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“…A prototype example is FN1 (fibronectin 1), which is highly overexpressed in PTC (11). Other examples include MET (12), DPP4 (dipeptidylpeptidase IV) (13), SER-PINA1 (␣ 1-antitrypsin) (14), KRT19 (keratin 19) (15), and LGALS3 (galectin-3) (16), which were overexpressed in all eight PTC samples. Several additional known genes were suggestive but did not meet the stringent criteria for Fig.…”

Section: Resultsmentioning

confidence: 99%

Gene expression in papillary thyroid carcinoma reveals highly consistent profiles

Huang

Prasad

Lemon

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

392

298

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Papillary thyroid carcinoma (PTC) is clinically heterogeneous. Apart from an association with ionizing radiation, the etiology and molecular biology of PTC is poorly understood. We used oligobased DNA arrays to study the expression profiles of eight matched pairs of normal thyroid and PTC tissues. Additional PTC tumors and other tissues were studied by reverse transcriptase-PCR and immunohistochemistry. The PTCs showed concordant expression of many genes and distinct clustered profiles. Genes with increased expression in PTC included many encoding adhesion and extracellular matrix proteins. Expression was increased in 8͞8 tumors for 24 genes and in 7͞8 tumors for 22 genes. Among these genes were several previously known to be overexpressed in PTC, such as MET, LGALS3, KRT19, DPP4, MDK, TIMP1, and FN1. The numerous additional genes include CITED1, CHI3L1, ODZ1, N33, SFTPB, and SCEL. Reverse transcriptase-PCR showed high expression of CITED1, CHI3L1, ODZ1, and SCEL in 6͞6 additional PTCs. Immunohistochemical analysis detected CITED1 and SFTPB in 49͞52 and 39͞52 PTCs, respectively, but not in follicular thyroid carcinoma and normal thyroid tissue. Genes underexpressed in PTC included tumor suppressors, thyroid function-related proteins, and fatty acid binding proteins. Expression was decreased in 7͞8 tumors for eight genes and decreased in 6͞8 tumors for 19 genes. We conclude that, despite its clinical heterogeneity, PTC is characterized by consistent and specific molecular changes. These findings reveal clues to the molecular pathways involved in PTC and may provide biomarkers for clinical use.

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“…This is a highly polymorphic glycoprotein and is a member of the protease inhibitor superfamily. Problete et al 52 reported that this protein was increased in papillary thyroid tumors, as detected with both immunocytochemical analysis and western blotting. A similar finding was reported by Lai et al 53 Because this gene was not found to be upregulated in goiter or normal tissue, it may serve as a selective marker for PTC.…”

Section: Discussion Genes Upregulated In Ptc Compared With Normalmentioning

confidence: 95%

TIMP1 and SERPIN‐A overexpression and TFF3 and CRABP1 underexpression as biomarkers for papillary thyroid carcinoma

et al. 2004

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Alpha1-Antitrypsin Expression in Human Thyroid Papillary Carcinoma

Cited by 24 publications

References 28 publications

Identification of SERPINA1 as single marker for papillary thyroid carcinoma through microarray meta analysis and quantification of its discriminatory power in independent validation

Identification of SERPINA1 as single marker for papillary thyroid carcinoma through microarray meta analysis and quantification of its discriminatory power in independent validation

Gene expression in papillary thyroid carcinoma reveals highly consistent profiles

TIMP1 and SERPIN‐A overexpression and TFF3 and CRABP1 underexpression as biomarkers for papillary thyroid carcinoma

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