Long noncoding RNA HOTAIR and Midkine as biomarkers in thyroid cancer

Abstract

Thyroid cancer is the most common endocrine malignancy, and its incidence is increasing. Differentiated thyroid cancer is the most common type and papillary thyroid carcinoma is the most common type of differentiated thyroid cancer. This work aimed to study long noncoding (Lnc) RNA homeobox transcript antisense RNA (HOTAIR) expression in plasma and serum midkine, a heparin binding growth factor, as biomarkers of thyroid cancer. This study included 27 thyroid cancer patients, 29 patients with benign thyroid disease and 26 individuals as normal controls. HOTAIR expression was assessed by real time polymerase chain reaction and midkine by ELISA. These biomarkers were elevated in thyroid cancer patients than patients with benign thyroid diseases and controls. Patients with thyroid cancer stage III had higher midkine levels in comparison to those with stage-I and stage-II (p < 0.001). Patients with grade II had higher midkine in comparison to those with grade I (p < 0.001). Statistically significant elevation of HOTAIR expression was found in stage III and stage II (p=0.001), compared to stage I. However, no difference was observed between stage II and stage III (p=0.533). There was no difference in both biomarkers in different histopathological types of thyroid cancer. ROC analysis was used for detection of thyroid cancer, midkine had AUC of 0.95 at a cutoff 897.5 pg/ml with a sensitivity of 98.0%, and specificity of 81.5% (p < 0.001). HOTAIR had AUC of 1 at a cutoff 11.8-fold change with a sensitivity and specificity of 100 %, (p < 0.001). We concluded that HOTAIR has high sensitivity and specificity in detection of thyroid cancer. It was correlated with tumor stage but not with histopathological types.