LAMB3 and TACSTD2, both highly expressed in salivary gland mucoepidermoid carcinoma, represent potential diagnostic biomarkers and therapeutic targets

Abstract

Salivary mucoepidermoid carcinoma (MEC) is the most common malignant tumor in major and minor salivary glands. The CRTC1-MAML2 or CRTC3-MAML2 gene arrangements, which occur in up to 80% of primary salivary glands with MEC, are the major oncogenic drivers of MEC carcinogenesis. However, the molecular consequences of these fusions remain unknown. We sought to identify the key functional genes involved in MEC, then characterize biomarkers with potential therapeutic relevance. We analyzed the gene expression profiles of two primary tumors (fusion-positive HCM-MEC020T and fusion-negative HCM-MEC030T); we compared them with the profiles of the established cell line HCM-MEC010 (derived from CRTC1-MAML2 fusion-positive MEC) and fibroblast cells derived from an HCM-MEC010 patient (non-tumor control cells). Fifty-three genes were identified as commonly expressed genes among the top 500 highly expressed genes in MEC but not in fibroblasts. Among these 53 genes, we focused on LAMB3 and TACSTD2, which are not predicted to be CRTC1/CRTC3-MAML2 target genes. LAMB3 (laminin subunit beta-3) is the basement membrane protein in normal salivary glands. TACSTD2 encodes a membrane protein associated with calcium signaling. To investigate the relationship between gene expression patterns and MEC pathological grade, we performed immunohistochemical staining of 13 MEC samples. LAMB3 and TACSTD2 proteins were expressed in the tumor cells of MEC samples (LAMB3, 12/13; TACSTD2, 13/13) but not in surrounding stromal cells. Although there were no statistically significant differences in LAMB3 or TACSTD2 expression among pathological grades, further studies are needed to elucidate the value of LAMB3 and TACSTD2 in clinical applications.