Expressions of ezrin, ERK, STAT3, and AKT in tongue cancer and association with tumor characteristics and patient survival

Abstract

Background Ezrin, ERK, STAT3, and AKT are proteins that are overexpressed in various types of cancer, although their expressions in tongue cancer has received less focus. This study aimed to address associations between the expression levels of these proteins and with characteristics of the tumor and patient survival. Methods We performed immunohistochemical staining of ezrin, ERK, STAT3, and AKT in tumors from patients with tongue carcinoma in situ (CIS, n = 17) and tongue squamous cell carcinoma (SCC, n = 46). Statistical differences between the SCC versus the CIS cohorts were estimated by calculations of bivariate odds ratios of low versus high expression of the proteins. Fisher's exact tests were used to appraise interassociations between the proteins, as well as expression levels versus patient and tumor characteristics. Survival based on Kaplan–Meier statistics in combination log‐rank tests were used to address potential effects of the patient and tumor characteristics versus 5‐year survival rate. Results The relative high: low expression of all four proteins in the two cohorts differed, and particularly ERK was markedly overexpressed in the SCC versus the CIS cohort (odds ratio = 45.3, p < .01). The relative high: low expression each protein versus patient and tumor characteristics; showed associations between AKT expression and T stage (p = .002) plus node metastases (p = .12), and between ERK expression and drinking (p = .01) and smoking history (p = .01). There was no significant difference observed between ERK and the three other molecules, nor any significant difference between the degree of expression of each protein and the 5‐year disease‐specific survival rate. Conclusion Ezrin, ERK, STAT3, and AKT appear to be involved in the progress from carcinoma in situ in the tongue into squamous cell carcinoma. ERK in particular is overexpressed, suggesting that ERK may be a novel therapeutic target for preventing tongue cancer.

Can Immunoexpression of Cancer Stem Cell Markers Prognosticate Tongue Squamous Cell Carcinoma? A Systematic Review and Meta-Analysis

“…No citations were identified during the grey literature search. Only six articles were considered for the second phase evaluation [26,[29][30][31][32][33]. Four CSC markers such as B lymphoma Mo-MLV insertion region 1 (BMI), Nanog homeobox (NANOG), Octamer-binding Transcription Factor-4 (OCT4), and Cluster of Differentiation 44 (CD44) have been studied by Rodrigues et al [34].…”

“…Tyrosine-protein kinase Met (c-MET) has been studied by two authors [29,30], and Sex Determining Region Y HMG-box 2 (SOX2) has been investigated by another two authors [31,33]. Signal Transducer and Activator of Transcription 3 (STAT3) was investigated in a single study [32]. Figure 1 presents the PRISMA flow chart.…”

“…We have identified six observational cross-sectional studies [29][30][31][32][33][34] associating the immunoexpression of seven CSC markers (c-MET, NANOG, OCT4, BMI, SOX2, STAT3, CD44) with clinicopathological features and outcomes (Tables 1 and 2). Out of the seven CSC markers, there were three surface markers [29][30][31], and the rest were transcription markers [31][32][33][34]. These studies were conducted in the Korean [29,30], Brazilian [34], Chinese [31][32][33], and Japanese [32] populations.…”

“…Out of the seven CSC markers, there were three surface markers [29][30][31], and the rest were transcription markers [31][32][33][34]. These studies were conducted in the Korean [29,30], Brazilian [34], Chinese [31][32][33], and Japanese [32] populations. All the studies were based on a small cohort of fewer than 100 subjects.…”

“…The age range of participants could not be determined because of the differences in reporting. Tumor size was reported in all the studies [29][30][31][32][33][34], where the early stage of presentation of TSCC was more frequent compared to the advanced stage. Grading was reported in only five studies [29][30][31][32][33], where the prevalence of moderate to poor grading was observed [31][32][33].…”