Dysregulation of KRT19, TIMP1, and CLDN1 gene expression is associated with thyroid cancer

Thyroid nodules are the main indicators of thyroid cancer, their malignancy is evaluated by cytological analysis and imaging technology, however, there are still cases where the result is not enough to classify thyroid cancer. Therefore, there is a necessity for accurate molecular biomarkers to collaborate in the diagnosis. Here, we analyzed the mRNA relative expression of CLDN1, TIMP1, and KRT19 genes in FNA of malignant (n = 48) and benign (n = 49) thyroid nodules by RT-qPCR analysis to assess their predictive value as cancer biomarkers. We identified a significant overexpression of the three transcripts in malignant nodules, therefore, the evaluation of their predictive capacity to distinguish between benign and malignant nodule as individual biomarkers were evaluated by logistic regression tests, obtaining promising prediction results to rule out cancer; later by random forest to create a stronger model, we included expression results with clinicopathological characteristics, the best model consists of the three-mRNA level expression with patient's history of cancer (AUC = 0.821, accuracy = 85.4% and sensitivity of 81.1%). These results demonstrate a dysregulated expression of CLDN1, KRT19 and TIMP1 in thyroid cancer, thus, represent a promising panel of biomarkers to be evaluated in indeterminate thyroid nodules.