S100A7 overexpression is a predictive marker for high risk of malignant transformation in oral dysplasia

Abstract

Early detection of oral lesions (OLs) at high risk of cancer development is of utmost importance for intervention. There is an urgent unmet clinical need for biomarkers that allow identification of high-risk OLs. Recently, we identified and verified a panel of five candidate protein biomarkers namely S100A7, prothymosin alpha, 14-3-3f, 14-3-3r and heterogeneous nuclear ribonucleoprotein K using proteomics to distinguish OLs with dysplasia and oral cancers from normal oral tissues. The objective of our study was to evaluate the potential of these candidate protein biomarkers for identification of oral dysplastic lesions at high risk of cancer development. Using immunohistochemistry, we analyzed expressions of these five candidate protein biomarkers in 110 patients with biopsy-proven oral dysplasia and known clinical outcome and determined their correlations with p16 expression and HPV 16=18 status. Kaplan-Meier survival analysis showed reduced oral cancer-free survival (OCFS) of 68.6 months (p 5 0.007) in patients showing cytoplasmic S100A7 overexpression when compared to patients with weak or no S100A7 immunostaining in cytoplasm (mean OCFS 5 122.8 months). Multivariate Cox regression analysis revealed cytoplasmic S100A7 overexpression as the most significant candidate marker associated with cancer development in dysplastic lesions (p 5 0.041, hazard ratio 5 2.36). In conclusion, our study suggested the potential of S100A7 overexpression in identifying OLs with dysplasia at high risk of cancer development.The development of oral squamous cell carcinoma (OSCC) is a multistep process, wherein frank malignancy is often preceded by oral lesions (OLs).1 Histological assessment of a biopsy with evidence of dysplasia is considered as the gold standard for determining the risk of malignant transformation.2-5 Increasing grade of dysplasia (mild=moderate=severe) has been associated with a high rate of malignant transformation; however, the progression rates vary from 6 to 36%. This

DNA damage marker phosphorylated histone H2AX is a potential predictive marker for progression of epithelial dysplasia of the oral cavity

“…Indeed, in patients with severe OD, the majority of specimens with high p16 expression had confirmed HPV infection. Consistent with previous reports that only a small proportion of patients with OSCC (<5%) were infected with HPV 17 and that p16 was a poor predictive marker of OD, 8,18 p16 was not associated with increasing histological grade of OD nor progression in this cohort. Other novel senescence markers assessed in this study did not show significant changes in expression by grade of OD or progression status.…”

Anticancer activity of pyrithione zinc in oral cancer cells identified in small molecule screens and xenograft model: Implications for oral cancer therapy

“…In support of cellular signaling cascades and novel proteins suggested as targets of PYZ in OSCCs, our data in human OSCCs and dysplasia clinical samples have demonstrated their relevance in development and progression of oral carcinogenesis (Kaur et al., 2014, 2013; Matta et al., 2008; Ralhan et al., 2009a; Tripathi et al., 2010; Winter et al., 2011). We showed OSCC patients showing overexpression of 14‐3‐3σ, 14‐3‐3ζ and/or decreased expression of membranous β‐catenin revealed reduced disease free survival.…”

“…Serial FFPE tissue sections (4 μm thickness) of tumors from PYZ treated and vehicle control group mice xenografts were deparaffinized in xylene, hydrated through graded alcohol series, antigen was retrieved by microwave treatment, endogenous peroxidase activity was blocked and non‐specific binding was blocked using normal horse serum (10%) as described earlier (Kaur et al., 2014). The sections were incubated with anti‐β‐catenin antibodies (0.2 μg/ml) (Santa Cruz Biotechnology Inc., Santa Cruz, CA) for 1 h at room temperature.…”

S100A7 promotes the migration, invasion and metastasis of human cervical cancer cells through epithelial-mesenchymal transition

“…S100A7 expression can serve as a biomarker for identifying dysplastic lesions at high risk of cancer development [20, 30]. And S100A7 overexpression, as an important risk factor, associated with reduced disease-free survival of OSCC patients [11].…”