Serum lncRNA PVT1 and Its Targets miR-146a and SIRT1 as Biomarkers for the Early Detection of Breast Cancer and Its Metastasis.

Abstract

Early detection of breast cancer (BC) and its metastasis greatly improves the patients' outcomes. The long noncoding RNA plasmacytoma variant translocation 1 (PVT1) and its targets, microRNA-146a and sirtuin 1 (SIRT1), affect BC development; however, their predictive abilities in early detection of BC and its metastatic potential are largely unknown. This study investigated serum PVT1, miR-146a, and SIRT1 as potential diagnostic and predictive biomarkers for BC and its metastasis. 120 BC patients, 40 breast fibroadenoma (BFA) patients, and 80 healthy volunteers were enrolled. An upregulation of serum PVT1 expression and SIRT1 protein levels was observed in BC patients compared to controls and BFA patients. miR-146a was downregulated in BC and BFA patients compared to controls, with lower levels in BFA compared to BC. Metastatic BC patients showcased higher PVT1 and SIRT1 and lower miR-146a levels than the nonmetastatic group. PVT1 and miR-146a were associated with the risk of developing BC among healthy controls. Combining PVT1 and miR-146a in a predictive panel showed substantial diagnostic accuracy for BC (area under the curve [AUC] = 0.91, 95% CI = 0.87-0.95). Only PVT1 was a predictor of the risk of developing BC among BFA cases and the risk of metastasis among BC patients. In BC, PVT1 was negatively correlated with miR-146a and positively correlated with SIRT1 and invasive lobular tumor type. Conclusively, our results highlight the PVT1/miR-146a/SIRT1 trajectory as a potential biomarker for early diagnosis and prognosis of BC. The study introduces the PVT1/miR-146a panel as an excellent biomarker for early BC diagnosis and uncloaks the predictive power of PVT1 in terms of breast tumor malignancy and metastatic tendency.