Prognostic and Clinicopathological Significance of the Aberrant Expression of β-Catenin in Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

Pablo Ramos-García,Miguel Á González-Moles

doi:10.3390/cancers14030479

Pablo Ramos-García, Miguel Á González-Moles

Open Access

https://doi.org/10.3390/cancers14030479

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Abstract

This systematic review and meta-analysis aims to evaluate the prognostic and clinicopathological significance of the aberrant expression of β-catenin (assessed through the immunohistochemical loss of membrane expression, cytoplasmic and nuclear expression) in oral squamous cell carcinoma (OSCC). We searched for primary-level studies published before October-2021 through PubMed, Embase, Web of Science, Scopus, and Google Scholar, with no limitation in regard to their publication date or language. We evaluated the methodological quality and risk of bias of the studies included using the QUIPS tool, carried out meta-analyses, explored heterogeneity and their sources across subgroups and meta-regression, and conducted sensitivity and small-study effects analyses. Forty-one studies (2746 patients) met inclusion criteria. The aberrant immunohistochemical expression of β-catenin was statistically associated with poor overall survival (HR = 1.77, 95% CI = 1.20-2.60, p = 0.004), disease-free survival (HR = 2.44, 95% CI = 1.10-5.50, p = 0.03), N+ status (OR = 2.39, 95% CI = 1.68-3.40, p < 0.001), higher clinical stage (OR = 2.40, 95% CI = 1.58-3.63, p < 0.001), higher tumour size (OR = 1.76, 95% CI = 1.23-2.53, p = 0.004), and moderately-poorly differentiated OSCC (OR = 1.57, 95% CI = 1.09-2.25, p = 0.02). The loss of β-catenin in the cell membrane showed the largest effect size in most of meta-analyses (singularly for poor overall survival [HR = 2.37, 95% CI = 1.55-3.62, p < 0.001], N+ status [OR = 3.44, 95% CI = 2.40-4.93, p < 0.001] and higher clinical stage [OR = 2.51, 95% CI = 1.17-5.35, p = 0.02]). In conclusion, our findings indicate that immunohistochemical assessment of the aberrant expression of β-catenin could be incorporated as an additional and complementary routine prognostic biomarker for the assessment of patients with OSCC.

Highlights

Oral cancer is a growing worldwide public health problem, presenting an incidence of 377,713 new cases and 177,757 deaths per year (GLOBOCAN, IARC, WHO) [1]
In this systematic review and meta-analysis on 41 studies and 2746 oral squamous cell carcinoma (OSCC) patients we demonstrate that the aberrant expression of β-catenin—mainly the immunohistochemical analysis of its loss in the cell membrane— behaves as a prognostic biomarker, significantly associated with poor survival, essentially linked to the increased risk for the development of lymph node metastases, higher tumour size and clinical stage in these patients
The results of our systematic review and meta-analysis of 41 studies and 2746 patients with Oral squamous cell carcinoma (OSCC) show that aberrant expression of β-catenin is a poor prognostic factor in OSCC associated with a significant decrease in overall survival (p = 0.004) and disease-free survival (p = 0.03)

Summary

Introduction

Oral cancer is a growing worldwide public health problem, presenting an incidence of 377,713 new cases and 177,757 deaths per year (GLOBOCAN, IARC, WHO) [1]. OSCC is a complex and heterogeneous disease in molecular terms [1,2], being accepted in recent years that at least two genetic subclasses should be distinguished, determined by their association with human papillomavirus (HPV) infection: HPV-positive tumours and HPV-negative tumours, with differential risk profile patterns [2]. In both subgroups, a male predilection is currently accepted. The prognostic value of molecular biomarkers is attracting considerable research interest and, in this sense, recent advances are suggesting a potential oncogenic and prognostic role for β-catenin in OSCC [3]

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