Evaluation of Salivary KCNJ3 mRNA Levels in Breast Cancer: A Case–control Study and in silico Analysis

Abstract

Background: Breast cancer (BC) is considered the most malignant and central cancer-related death among women worldwide. There is an essential need to discover new methods for developing noninvasive and low-cost diagnoses. The present study examines the expression of KCNJ3 which acts as a biomarker for detecting BC in the saliva of BC patients compared to controls. Methods: The mRNA expression level of KCNJ3 has been evaluated. Forty-three unstimulated whole saliva samples from BC patients and forty-three salivary samples from healthy controls were collected. The mRNA level was measured using quantitative real-time polymerase chain reaction (qRT-PCR). Furthermore, the protein-protein interaction network in which KCNJ3 is involved was obtained. In silico analysis was applied to predict the possible molecular mechanisms of KCNJ3 in BC development. Results: Differentially expressed KCNJ3 was statistically significant between BC patients and controls (p<0.001). The sensitivity and specificity of KCNJ3 mRNA in BC detection were 76.74% and 94.95%, respectively. Receiver operating characteristic (ROC) curve analysis of KCNJ3 mRNA revealed that Area under the curve (AUC) was 0.923 (95% Confidence Interval (CI): 0.866-0.979). AUCs of ROC curve analysis were 0.743 (95% CI: 0.536-0.951), 0.685 (95% CI: 0.445-0.925), and 0.583(95% CI: 0.343-0.823) for differentiation stage I from stage III, stage I to stage II and finally stage II from stage III, respectively. Furthermore, the GABAergic synapse signaling pathway was suggested as a potential pathway involved in BC development. Conclusion: Salivary levels of KCNJ3 could be considered a potential diagnostic biomarker with high sensitivity and specificity for BC detection.