Increasing the Number of Thyroid Lesions Classes in Microarray Analysis Improves the Relevance of Diagnostic Markers

BackgroundGenetic markers for thyroid cancers identified by microarray analysis have offered limited predictive accuracy so far because of the few classes of thyroid lesions usually taken into account. To improve diagnostic relevance, we have simultaneously analyzed microarray data from six public datasets covering a total of 347 thyroid tissue samples representing 12 histological classes of follicular lesions and normal thyroid tissue. Our own dataset, containing about half the thyroid tissue samples, included all categories of thyroid lesions. Methodology/Principal Findings Classifier predictions were strongly affected by similarities between classes and by the number of classes in the training sets. In each dataset, sample prediction was improved by separating the samples into three groups according to class similarities. The cross-validation of differential genes revealed four clusters with functional enrichments. The analysis of six of these genes (APOD, APOE, CLGN, CRABP1, SDHA and TIMP1) in 49 new samples showed consistent gene and protein profiles with the class similarities observed. Focusing on four subclasses of follicular tumor, we explored the diagnostic potential of 12 selected markers (CASP10, CDH16, CLGN, CRABP1, HMGB2, ALPL2, ADAMTS2, CABIN1, ALDH1A3, USP13, NR2F2, KRTHB5) by real-time quantitative RT-PCR on 32 other new samples. The gene expression profiles of follicular tumors were examined with reference to the mutational status of the Pax8-PPARγ, TSHR, GNAS and NRAS genes. Conclusion/Significance We show that diagnostic tools defined on the basis of microarray data are more relevant when a large number of samples and tissue classes are used. Taking into account the relationships between the thyroid tumor pathologies, together with the main biological functions and pathways involved, improved the diagnostic accuracy of the samples. Our approach was particularly relevant for the classification of microfollicular adenomas

Anthropologie et biologie médicale, application au goitre et au crétinisme endémiques, pays Bwa (Mali)

ANTHROPOLOGY AND MEDICAL BIOLOGY, APPLICATION TO THE ENDEMIC GOITER AND ENDEMIC CRETINISM, BWA REGION (MALI) Summary. — The study is concerned with the dispersion, the importance and the causes of the endemic goiter and cretinism in a village of Mali. The methods which are used there, relied on a very accurate definition of the population, on the precision of the diagnosis, on the measuring out of the serum, of the urine and of the food, on blood tests, bringing to the fore all the genetic markers known. The prevalence of the goiter is of 71,21 % for the men and of 89,09 % for the women. Moreover the hormones TSH and T4 playing a very discriminant role between goitrous and non goitrous. The genetic factor appears here very probable. As for the cretinism its prevalence is certainly of 1%.Résumé. — L'étude porte sur la dispersion, l'importance et les causes du goitre et du crétinisme endémiques dans un village du Mali. Les méthodes utilisées se sont appuyées sur une définition très précise de la population, sur la rigueur des diagnostics, sur les dosages sériques, urinaires et alimentaires, sur les analyses sanguines mettant en évidence l'ensemble des marqueurs génétiques connus. La prévalence du goitre est de 71,21 % chez les hommes et de 89,09 % chez les femmes, les hormones TSH et T4 jouant par ailleurs un rôle très discriminant entre goitreux et non goitreux, le facteur génétique apparaît ici très probable. Quant au crétinisme, sa prévalence est vraisemblablement de l'ordre de 1 %.Bellis G., Chaventré André, Roux F., Bisset J.-P., Chastin I., Rhaly A. Ag, Margotat A., Malthiery Y. Anthropologie et biologie médicale, application au goitre et au crétinisme endémiques, pays Bwa (Mali). In: Bulletins et Mémoires de la Société d'anthropologie de Paris, XIV° Série. Tome 5 fascicule 1-2, 1988. pp. 47-60