The Signal Transducer IL6ST (gp130) as a Predictive and Prognostic Biomarker in Breast Cancer

Abstract

Novel biomarkers are needed to continue to improve breast cancer clinical management and outcome. IL6-like cytokines, whose pleiotropic functions include roles in many hallmarks of malignancy, rely on the signal transducer IL6ST (gp130) for all their signalling. To date, 10 separate independent studies based on the analysis of clinical breast cancer samples have identified IL6ST as a predictor. Consistent findings suggest that IL6ST is a positive prognostic factor and is associated with ER status. Interestingly, these studies include 4 multigene signatures (EndoPredict, EER4, IRSN-23 and 42GC) that incorporate IL6ST to predict risk of recurrence or outcome from endocrine or chemotherapy. Here we review the existing evidence on the promising predictive and prognostic value of IL6ST. We also discuss how this potential could be further translated into clinical practice beyond the EndoPredict tool, which is already available in the clinic. The most promising route to further exploit IL6ST’s promising predicting power will likely be through additional hybrid multifactor signatures that allow for more robust stratification of ER+ breast tumours into discrete groups with distinct outcomes, thus enabling greater refinement of the treatment-selection process.

The IL6-like Cytokine Family: Role and Biomarker Potential in Breast Cancer

“…Lastly, the positive correlation between gp130/IL6ST expression and ER has been well established, as we recently reviewed [214] (also see Section 5.3). In short, evidence suggests that gp130/IL6ST might act as a robust surrogate marker of active oestrogenrelated signalling.…”

“…We also showed that IL6ST has been included in four different multifactor signatures (including the clinically-available EndoPredict assay), where gp130/IL6ST also served as a positive prognostic factor for ER+ BC [214]. These multigene signatures enable stratification of BC patients into prognostic groups with differing risks of recurrence and rates of response to different therapeutic strategies, so they could aid treatment selection.…”

“…As the cornerstone of all signalling by cytokines in the IL6-like family, the shared signal transducer gp130/IL6ST holds particular potential as both a therapeutic target and a candidate biomarker. We recently reviewed the extensive evidence of gp130/IL6ST as a promising predictor in BC [214]. In short, in recent years ten different independent studies based on the analysis of clinical BC samples have shown the value of gp130/IL6ST as a prognostic and/or predictive biomarker.…”

“…In short, in recent years ten different independent studies based on the analysis of clinical BC samples have shown the value of gp130/IL6ST as a prognostic and/or predictive biomarker. Six studies reported that gp130/IL6ST serves as an independent marker and is, specifically, a positive prognostic marker in BC; its expression is significantly correlated with ER expression and better prognosis, and inversely correlated with adverse events such as invasion, metastasis and recurrence [214].…”

Special Issue “Cancer Biomarker Research and Personalized Medicine”

“…Although biomarkers have been defined according to specific applications, biomarkers may also meet multiple criteria for different uses. Numerous papers contributed to this Special Issue deal with biomarkers that fall into this category, including studies involving colorectal [18] and breast [19][20][21] cancers.…”