AXIN2 and SNAIL expression predict the risk of recurrence in cutaneous squamous cell carcinoma after Mohs micrographic surgery

Abstract

Recurrence is a common complication observed during cutaneous squamous cell carcinoma (cSCC) treatment; however, biomarkers for predicting recurrence in cSCC remain unknown. The present study aimed to investigate the predictive value of axis inhibition protein 2 (AXIN2) and SNAIL expression in cSCC recurrence. AXIN2 and SNAIL expression was evaluated using immunohistochemistry in 111 cSCC tissue samples obtained from 18 patients who presented recurrence (recurrence interval, 1-91 months) and 93 patients who did not experience recurrence following Mohs micrographic surgery (MMS) during the follow-up period (156 months). Nomogram construction was performed using patients' clinicopathological characteristics and AXIN2 and SNAIL protein expression. The results demonstrated that high AXIN2 (histoscore >100) and SNAIL (histoscore >100) expression was detected in 35 and 44 cSCC tissues, respectively. Furthermore, the expression levels of AXIN2 and SNAIL were significantly associated in patients with cSCC (P=0.001). AXIN2 and SNAIL expression levels were significantly associated with tumor size (P=0.021 and P=0.044, respectively) and recurrence of cSCC (P=0.017 and P=0.042, respectively). In addition, the results of the Kaplan-Meier curve analysis revealed that recurrence-free survival was significantly associated with tumor size (P=0.025), differentiation status (P<0.001), AXIN2 expression (P=0.001) and SNAIL expression (P=0.001). Furthermore, the results of the multivariate analysis demonstrated that age (P=0.043), AXIN2 expression (P=0.001) and SNAIL expression (P=0.045) were independent risk factors for cSCC recurrence in the present cohort. A nomogram for predicting the 1-, 2-, 3-, and 5-year recurrence-free survival was developed for patients with cSCC by including independent risk factors with a concordance index of 0.75. The results suggested that high AXIN2 and SNAIL expression may be considered as potential risk factors for cSCC recurrence. This nomogram may therefore be useful to assess the probability of recurrence in patients with cSCC following MMS.

The Expression of Selected Wnt Pathway Members (FZD6, AXIN2 and β-Catenin) in Canine Oral Squamous Cell Carcinoma and Acanthomatous Ameloblastoma

“…We noticed overexpression of AXIN2 in both CAA as well as COSCC when compared to a normal gingiva. In human ameloblastoma, there was also strong immunostaining of AXIN2 in comparison to a normal oral mucosa [55], and high expression levels of AXIN2 in human SCC were associated with tumor size and recurrence [56]. Moreover, increased levels of AXIN2 were highly correlated with the malignant transformation of an oral leukoplakia in humans [57], indicating possibly similar associations in canine oral tumors.…”

Snail maintains the stem/progenitor state of skin epithelial cells and carcinomas through the autocrine effect of the matricellular protein Mindin

“…Only a few cells in the tumor express Snail, so the number of cells secreting Mindin is limited and correlates with the number of cancer stem cells. Interestingly, in aggressive tumors, Snail and Mindin expression is increased along with the number of cancer stem cells (Hojo et al, 2018b;Kang et al, 2020;Zhao et al, 2020); 2. The ECM binding nature of Mindin substantially restricts its diffusion and thus limits the number of cells that is exposed to this matricellular protein; 3.…”

Gene expression profiling to explore the protective effect of Antrodia cinnamomea compound decoction on PM2.5-induced lung inflammation in rats

“…The PLC-β class of phospholipases is composed of four isozymes (β1-β4) encoded by different genes [32]. PLC-β1 is highly expressed in neuronal tissue and may play an important role in neuroendocrine growth factor-stimulated cell proliferation [37,38]. PLC-β blockade of signaling may be a valuable method to inhibit cell growth and metastasis.…”

“…Axis inhibition protein 2 (AXIN2) is a downstream target of the Wnt signaling pathway, which plays an important role in the regulation of β-catenin stability and its involvement in various cellular functions [39,40]. Previous studies suggest that AXIN2, one of the downstream targets of T cytokines/lymphopoietic enhancers of the Wnt signaling pathway, may have oncogenic effects [37]. AXIN2 has been shown to be upgraded in various types of cancer [38].…”