Low Expression of a Circular Transcript of the Apoptosis Regulator Gene BOK Is Associated with Unfavorable Prognosis...

Background: We recently identified multiple alternative circRNAs generated through alternative circularization of primary transcripts of the BCL2-related ovarian killer (BOK) gene. In the present study, we evaluated the prognostic potential of a recently discovered BOK circRNA, namely circ-BOK-6, in breast cancer (BC). Methods: Tumor specimens from a cohort of 172 female BC patients were analyzed, including paired adjacent non-cancerous breast tissue from 44 cases. circ-BOK-6 expression levels were quantified using an in-house-developed quantitative real-time PCR assay, followed by comprehensive biostatistical and survival analyses. Results: circ-BOK-6 expression differed between matched tumor and normal breast tissues. However, no significant associations were observed between circ-BOK-6 expression and BC clinicopathological characteristics. Importantly, after splitting at the median value, low circ-BOK-6 expression was associated with poorer disease-free survival (DFS) and overall survival (OS). Multivariate Cox regression analysis further demonstrated that the prognostic value of low circ-BOK-6 expression was independent of established prognostic factors included in the models, including the prognostic stage or the molecular subtype and the anatomic stage of the disease. Additionally, stratified analyses based on these key prognostic parameters revealed that low circ-BOK-6 expression retains prognostic significance within specific patient subgroups. Conclusions: These findings suggest that low circ-BOK-6 expression represents a promising independent biomarker of adverse prognosis in BC.