Identification of Candidate Target Genes and Immune Cells in Oral Squamous Cell Carcinoma.

BACKGROUND: The advance of new treatment strategies for more effective management of oral cancer requires identification of novel biological targets. Therefore, the purpose of this study is to identify novel biomarkers associated with oral tumorigenesis and prognostic signature by comparing gene expression profile of oral squamous cell carcinomas (OSCCs). METHODS: Four datasets including GSE25099, GSE30784, GSE37991, and GSE41613 were collected from Gene Expression Omnibus (GEO) database. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, Cox model analysis, identification of key genes, and Kaplan-Meier analysis were also performed. The xCell was utilized to analyze the infiltration levels of immune cells. RESULTS: A total of 235 differentially expressed genes (DEGs) were found to be dysregulated in OSCC. These genes were mainly enriched in ECM receptor interaction and focal adhesion. Cox regression analysis identified 10 genes considered as key genes. Kaplan-Meier analysis showed that low expression of SERPINE1 (also known as PAI-1), high expression of CD1C, and C-X3-C motif chemokine receptor 1 (CX3CR1) were associated with well prognostic status in OSCC patients. In addition, we constructed a 3-immune-cell signature (myeloid dendritic cell, T cell CD4+ central memory, and common myeloid progenitor) that may be used to predict the survival status of OSCC patients. CONCLUSION: Three key genes and 3-immune-cell signature were potential biomarkers for the prognosis of OSCC, and they may serve as potential targets for the treatment of OSCC patients.

Elevated microRNA-145 inhibits the development of oral squamous cell carcinoma through inactivating ERK/MAPK signaling pathway by down-regulating HOXA1.

Background: Oral cancer is one of the most frequent solid cancers worldwide, and oral squamous cell carcinoma (OSCC) constitutes approximately 90% of oral cancers. The discovery of reliable prognostic indicators would be a potential strategy for OSCC treatment. In the present study, we aim to explore the underlying mechanism by which microRNA-145 (miR-145) affected OSCC. Methods: Forty-eight patients diagnosed with OSCC were enrolled to obtain the OSCC tissues and adjacent normal tissues. The targeting relationship between miR-145 and Homeobox A1 (HOXA1) was verified. In order to assess the effects of miR-145 in OSCC and the detailed regulatory mechanism, the SCC-9 cell line was adopted, in which expression of miR-145 and HOXA1 were altered by transfection. Then, a series of in vitro and in vivo experiments were performed to evaluate the cell viability, migration, invasion, and tumor growth. Results: miR-145 was poorly expressed and HOXA1 was highly expressed in OSCC. HOXA1 was verified as a target of miR-145 to mediate the activation of the extracellular signal-regulated kinase/mitogen activated protein kinase (ERK/MAPK) signaling pathway. In the circumstance of miR-145 elevation or HOXA1 depletion, the SCC-9 cell line manifested with inhibited cell viability, invasion, and migration in vitro, coupled with reduced tumor growth in vivo, with a decreased expression of ERK/MAPK signaling pathway-related genes/proteins. Conclusion: These findings suggested that miR-145 can inhibit HOXA1 to inactivate the ERK/MAPK signaling pathway, thereby suppressing OSCC cell proliferation, migration, and invasion to further inhibit the development of OSCC, highlighting a novel therapeutic target for the OSCC treatment.

Circulating Anti-Matrix Metalloproteinase-7 Antibodies May Be a Potential Biomarker for Oral Squamous Cell Carcinoma.

PURPOSE: The present study was conducted to evaluate the diagnostic and prognostic values of serum autoantibody against matrix metalloproteinase-7 (MMP-7) in patients with oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Anti-MMP-7 antibodies were measured in sera from 204 patients with OSCC and 212 normal controls using enzyme-linked immunosorbent assay, and clinicopathologic characteristics were correlated. Prognostic consequence was assessed with Kaplan-Meier curve and log-rank tests using Cox proportional hazard models. To check whether anti-MMP-7 antibody was related to tumor associated antigen, real-time polymerase chain reaction and western blot were used to measure MMP-7 mRNA and protein expression in tumor tissues from all 204 patients with OSCC. RESULTS: Serum anti-MMP-7 antibody was higher in patients with OSCC (P < .05), and those with poorly differentiated tumors had more anti-MMP-7 antibody than those with well to moderate tumor differentiation (P < .01, P < .01, respectively). Patients with OSCC at late TNM stages (III, IV) and lymph node metastases had relatively higher serum anti-MMP-7 antibody levels than those with earlier stages (I, II) and those who lacked lymph node metastases (P < .05 for the 2 comparisons). OSCC prediction sensitivity as measured by receiver operating characteristics analysis was 0.485 and specificity was 0.896 (area under the curve, 0.761; 95% confidence interval, 0.716 to 0.806). Cox analysis showed that serum anti-MMP-7 antibody positivity independently predicted poor overall survival in patients with OSCC (hazard ratio, 1.82; 95% confidence interval, 1.07 to 4.61). MMP-7 mRNA and protein expression was increased in tumor tissues from patients with OSCC and high serum anti-MMP-7 antibody. CONCLUSION: Serum anti-MMP-7 antibody might be a novel diagnostic and prognostic biomarker for OSCC.