Transcriptome analysis discloses dysregulated genes in normal appearing tumor-adjacent thyroid tissues from patients with papillary thyroid carcinoma

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Histologically normal appearing tissue adjacent to the tumor (NAT) from PTC patients is commonly used as a control in thyroid cancer studies, but the molecular characteristics of NAT tissue are not well characterized. The aim of this study was to characterize the global gene expression profile of NAT and compare it with those of normal and tumor thyroid tissues. We performed RNA sequencing of three categories of thyroid tissue samples including NAT, normal thyroid (N), and PTC tumor (T). Transcriptome analysis shows that NAT presents a unique gene expression profile, which was not associated with sex and the presence of lymphocytic thyroiditis. Among the differentially expressed genes (DEGs) of NAT vs N, 247 coding genes and 6 noncoding genes have been reported as cancer genes, being involved in cell proliferation, apoptosis, and tumorigenesis. In addition, dysregulated expression of ribosomal and small RNAs was identified in NAT. IPA analyses revealed that “Cellular Response to Therapeutics, Cardiovascular Disease, Organismal Injury and Abnormalities, Cancer, and Cellular Movement” appeared as major dysregulated pathways in the NAT tissues. This study provides a comprehensive study of the PTC transcriptome, which provides improved insight into the complexity of gene expression changes during PTC tumorigenesis. Normal appearing thyroid tissue adjacent to the tumor samples (NAT, n=46) and paired PTC tumor tissue samples (T, n=16) were analyzed from 46 PTC patients. Among these PTC patients, there were 21 patients with co-existent lymphocytic thyroiditis (LT) (PTC/LT+) and 25 patients without LT (PTC/LT-). Normal thyroid tissue samples (N, n=12) were obtained from laryngeal cancer patients without thyroid lesions.