Prognostic Significance of Circular HER2 and Its Association with EMT Markers in Advanced Breast Cancer

Abstract

Introduction: Globally, breast cancer (BC) represents the most prevalent malignancy among females. In the field of epigenetic regulation, non-coding circular RNAs have recently been identified as key contributors to BC pathogenesis. Among this class, circular HER2 (Circ-HER2 ) has been documented to be overexpressed in various cancers, including BC. Particularly, in triple-negative breast cancer (TNBC), elevated Circ-HER2 expression correlates with increased metastatic potential, invasiveness, and cell proliferative capacity. Nevertheless, the precise molecular mechanisms through which Circ-HER2 is implicated in TNBC remains inadequately understood and further investigations are still needed. Consequently, this study aimed to investigate the Circ-HER2 gene expression profile in a sample of BC patients and to elucidate its association with other prognostic biomarkers and disease aggressiveness phenotypes. Patients and Methods: This study was conducted on 40 breast cancer patients, two tissue specimens were collected from each patient: one from the malignant tumor (MT) and the other sample from the corresponding adjacent, microscopically normal breast tissue (TAN). q-RT-PCR was employed for gene expression profiling of Circ-HER2, E-Cadherin, ILE2, and Twist1 in malignant as well as normal tissues. Results: Our results revealed a significant upregulation of Circ-HER2, ILE2, and Twist1 in malignant tissues compared to the matched adjacent normal tissues. Furthermore, Circ-HER2 expression demonstrated a statistically significant correlation with E-Cadherin expression, ILE2, and Twist1. However, when the TNBC patients analyzed separately, Circ-HER2 was significantly higher than E-Cadherin, while its expression was not significantly different than the other metastatic markers. Conclusion: In conclusion, the significant Circ-HER2 overexpression in breast cancer tissues, along with significant correlation of Circ-HER2 with increased levels of key EMT biomarkers, especially in TNBC patients, suggest a potential role for Circ-HER2 in promoting an aggressive, pro-metastatic phenotype in breast cancer. These findings provide preliminary clinical evidence supporting the oncogenic function of Circ-HER2 and underscore the need for further mechanistic investigations to delineate its precise molecular pathway and validate its potential as a prognostic biomarker or therapeutic target in breast cancer, particularly in the aggressive subtypes such as TNBC, where therapeutic options are limited.