Significance of migration-related genes (S100A9, MAGED4, C8orf30A, IL-8) in esophageal squamous cell carcinoma

Abstract

To identify any biomarkers related to the migration of esophageal squamous cell carcinoma (ESCC) cells, ESCC CE81T cells were used to establish the CE81T-1 subline, which demonstrates increased migration activity after Transwell screening and microarray analysis. Among the differentially expressed genes, S100A9 was most downregulated, and MAGED4, C8orf30A, and IL-8 were the most upregulated in CE81T-1 cells. The expression of these four genes at the mRNA level was validated using the ESCC CE81T and KYSE cell lines and clarified in ESCC specimens using real-time polymerase chain reaction. Among 60 pairs of ESCC specimens (normal and tumor specimens), the expression level of S100A9 mRNA was significantly lower in the tumor sections in comparison with the normal sections (p = 0.0228). In contrast, the expression level of IL-8 mRNA was significantly higher in the tumor sections in comparison with the normal sections (p = 0.0061). Furthermore, C8orf30A expression was significantly correlated with ESCC metastatic status (p = 0.0358) and associated with poorer survival (p = 0.036), as determined by Kaplan-Meier analysis. Functional studies revealed that S100A9 plays a suppressive role in the proliferation and migration of ESCC cells through the overexpression of ectopic S100A9 and small interfering RNA, as determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Transwell assays. Altogether, this study reveals that C8orf30A has the potential to be used as a novel biomarker for the prognosis for ESCC metastasis and survival. Furthermore, the IL-8 and S100A9 genes may have potential in ESCC diagnosis.