SPINK7 Expression Changes Accompanied by HER2, P53 and RB1 may be Potential Biomarkers to Predict Oral Squamous Cell Carcinoma at Molecular Level

Abstract Background. The oral squamous cell carcinoma (OSCC) affects more than 300,000 patients annually worldwide with a high morbidity rate (37.8%). Several tumor biomarkers have been suggested to anticipate outcome but results were poor. Changes of SPINK7 and associated proteins in precancerous oral lesions could lead to genomic instability and promote oncogenesis. Our aim was to evaluate SPINK7as apotential molecular biomarkerpredictive of OSCC stages, compared with well-known molecules altered in cancer: HER2,TP53, RB1, NFKB and CYP4B1. Methods.Oral biopsies from patientswith dysplasia (n=33), less invasive(n=28) andhighly invasiveOSCC (n=18) were collected. 20 cases with a clinical suspicion but normal mucosa confirmedwere included ascontrol. Gene expression of SPINK7, P53,RB, NFKBand CYP4B1 were quantified by qPCR.SPINK7 levels were correlated with a cohort of 330 patients from the TCGA. Also,SPINK7, HER2, TP53, and RB1, were evaluated by immunohistofluorescence. One-way Kruskal-Wallis test and Dunn's post-hocwith a p<0.05 significance were used to data analyze.Results.In OSCC, SPINK7wasdown regulated andP53, RB, NFKB and CYP4B1were up regulatedrespect tothe others groups (p<0.001). Also,SPINK7 expressionwasdiminished in patients of TCGA(p=2.10e-6). In less invasive OSCC,SPINK7 and HER2 proteinswere decreasedandTP53 and RB1 significantly increasedrespect todysplasia and highly invasivegroups (p<0.05).Conclusion. Our results suggest that SPINK7changes accompanied of HER2, P53 and RB1 can be used to classify the molecular stage of epithelial oral lesion inthe OSCC, allowing a more accuratediagnosis to molecular and histopathological level.