β-catenin: An important biomarker for wound healing

Biomarkers are naturally occurring molecules which can be used to predict, diagnose and indicate pathological or physiological processes.¹ Predictive biomarkers can be used to predict outcomes for wounds or provide the likelihood of benefit from treatment (Pichu et al. 2017).² Also, diagnostic biomarkers in wounds can be utilized to identify singular or multiple factors that have the potential to influence a clinical outcome. An indicative biomarker can be used to assess disease progression and response to therapy during treatments.³ This essay will focus on β-catenin as a predictive, diagnostic and indicative biomarker.

β-catenin is defined as a dual function protein responsible for both regulating and coordinating cell-to-cell adhesion and cell migration (Nelson and Nusse, 2004).⁴ The key protein which reacts with β-catenin to regulate its expression is called Adenomatous Polyposis Coli (APC).³ Recent research⁴ suggests that tissue homeostasis is dependent upon the essential multi-protein interactivity between APC and β-catenin. Therefore, the loss of APC protein function leads to a deregulated β-catenin nuclear accumulation.⁵ Ultimately, this dissociation and deregulation of the multi-protein complex can disrupt the processes of wound healing and thus prolong healing duration in wounds.⁶

According to recent research (Cai et al. 2017)⁷ tissue sampling of β-catenin can be utilized to predict contrasting outcomes in wound healing, such as the inhibition of epithelial cell and keratinocyte migration or the activation of abnormal fibroblast proliferation. The possibility for contrasting outcomes suggests that β-catenin has an important role in regulating wound size through either inhibiting or enhancing remodelling processes.⁸ Therefore, the relationship between the over-expression of β-catenin on the border of a non-healing wound could enable a predictive assessment for the extent to which wound healing may occur.⁹

According to recent research,^{1, 5} tissue sampling of β-catenin can be an effective diagnostic biomarker as this method of testing can identify areas of thickened, hyperproliferative and parakeratotic epidermis. Furthermore, detection of β-catenin can aid in the diagnosis of chronic wounds by indicating aberrant proliferation and inappropriate differentiation of cells in the borders of non-healing wounds.¹⁰

On the other hand, according to Shang et al.,¹¹ tissue sampling of β-catenin has limited standardized guidance for specimen retrieval, inadequate logistics of service-based diagnostics and subsequent requirement for the incorporation of established therapeutics into standard healthcare and clinical trial protocols.

Current research¹² suggests that tissue sampling of β-catenin presents as an indicative biomarker to the extent that early detection of abnormal levels of the biomarker could assist in preventing disease progression. However, this is dependent on the method of specimen retrieval and the availability of pharmacologic interventions such as Lithium and topical agents such as Asiaticoside Nitric Oxide gel which are suggested to stabilize β-catenin levels for optimum wound healing.¹³

Recent evidence¹³ suggests that up-regulation of β-catenin can accelerate the wound healing process. This notion is supported by previous evidence^{14, 15} by effectively controlling cell-to-cell adhesion and collective cell migration during the process of tissue remodelling.

Overall, tissue sampling of β-catenin guides treatment for non-healing foot ulcers to the extent that despite the drawbacks of lacking standardization of specimen retrieval, early detection of β-catenin could facilitate more personalized treatment protocols.¹⁶ This factor suggests potential for the clinical feasibility and utility of β-catenin sampling. In general, therefore, it seems that further clinical studies and evaluation are needed to establish the full extent to which tissue sampling of β-catenin is reliable and valid in non-healing wounds within a clinical setting.⁷ Large multicentre trials could help achieve this.⁸

The author is an editorial board member of the International Wound Journal.