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.

Aldosterone-producing adenomas (APA) is one of the causative factors of primary aldosteronism. Previous studies have suggested that there are somatic CTNNB1 mutations in APA, but the specific mechanism of CTNNB1 mutation in APA tumorigenesis and aldosterone secretion remains unclear. In the present study, human adrenocortical carcinoma cell line H295 R was used to establish stable CTNNB1 knockdown cell lines. Cell proliferation and aldosterone secretion of H295 R cells in response to angiotensin Ⅱ (Agn Ⅱ) were analyzed. We found that CTNNB1 knockdown reduced β-catenin expression and inhibited proliferation of H295 R cells. CTNNB1 knockdown inhibited Wnt/β-catenin signaling pathway and downregulated expression of downstream genes including axin 2, lymphoid enhancer binding factor 1 (LEF1), and cyclin D1. In addition, CTNNB1 knockdown decreased responses of H295 R cells to Agn Ⅱ and decreased aldosterone secretion. Our findings suggest that CTNNB1 knockdown can inhibit H295 R cell proliferation and decrease aldosterone secretion in the responses of H295 R cells to Ang II through inhibiting Wnt/β-catenin signaling pathway, indicating that targeting Wnt/β-catenin signaling pathway may be an important approach to decrease aldosterone secretion in the treatment of aldoster-producing adenomas.