Identification of key biomarkers for thyroid cancer by integrative gene expression profiles

Abstract

Thyroid cancer is a frequently diagnosed malignancy and the incidence has been increased rapidly in recent years. Despite the favorable prognosis of most thyroid cancer patients, advanced patients with metastasis and recurrence still have poor prognosis. Therefore, the molecular mechanisms of progression and targeted biomarkers were investigated for developing effective targets for treating thyroid cancer. Eight chip datasets from the gene expression omnibus database were selected and the inSilicoDb and inSilicoMerging R/Bioconductor packages were used to integrate and normalize them across platforms. After merging the eight gene expression omnibus datasets, we obtained one dataset that contained the expression profiles of 319 samples (188 tumor samples plus 131 normal thyroid tissue samples). After screening, we identified 594 significantly differentially expressed genes (277 up-regulated genes plus 317 down-regulated genes) between the tumor and normal tissue samples. The differentially expressed genes exhibited enrichment in multiple signaling pathways, such as p53 signaling. By building a protein–protein interaction network and module analysis, we confirmed seven hub genes, and they were all differentially expressed at all the clinical stages of thyroid cancer. A diagnostic seven-gene signature was established using a logistic regression model with the area under the receiver operating characteristic curve (AUC) of 0.967. Seven robust candidate biomarkers predictive of thyroid cancer were identified, and the obtained seven-gene signature may serve as a useful marker for thyroid cancer diagnosis and prognosis.