Serum-Based lncRNA ANRIL, TUG1, UCA1, and HIT Expressions in Breast Cancer Patients

Abstract

Breast cancer is a heterogeneous disease and is the most common and prevalent form of malignancy diagnosed in women. lncRNAs are found to be frequently dysregulated in cancer, and its expression plays a critical role in tumorigenesis. The study included 100 histopathologically confirmed, newly diagnosed untreated patients of invasive ductal carcinoma (IDC) of breast cancer patients and 100 healthy subjects. After blood collection, the serum was separated and total RNA was extracted, cDNA was synthesized using 100 ng of total RNA, and lncRNA (ANRIL, TUG1, UCA1, and HIT) expression was analyzed. Increased ANRIL (3.83-fold), TUG1 (7.64-fold), UCA1 (7.82-fold), and HIT (3.31-fold) expressions were observed in breast cancer patients compared to healthy controls. Relative expression of lncRNAs UCA-1 ( $p=0.010$ ) and HIT-1 ( $p<0.0001$ ) was significantly elevated in patients with advanced breast cancer stage compared to those with early-stage disease. While lncRNA TUG-1 expression was found to be higher in patients with early-stage tumors than those with advanced-stage tumors ( $p=0.06$ ), lncRNA ANRIL showed increased expression in patients with PR positive status ( $p=0.04$ ). However, we found a significant difference in lncRNA HIT expression in HER-2 positive breast cancer patients compared to HER-2 negative breast cancer patients ( $p=0.005$ ). An increase in the expression of serum lncRNAs ANRIL ( $p<0.0001$ ), UCA-1 ( $p=0.004$ ), and HIT ( $p<0.0001$ ) was observed in the distant organ metastatic breast cancer patients. In the ROC curve concerning lymph node involvement, the sensitivity and specificity of lncRNA HIT were 68% and 58%, respectively ( $p$ value = 0.007). In the ROC curve w.r.t. stages of disease, the sensitivity and specificity of lncRNA HIT were 80% and 50%, respectively ( $p$ value < 0.0001). Better sensitivity and specificity were observed for lncRNA HIT (sensitivity 91% and specificity 78%; $p$ value < 0.0001) and ANRIL (sensitivity 70% and specificity 60%; $p$ value < 0.0001) w.r.t distant organ metastases.