Expression Profiling of Extracellular Matrix Genes Reveals Global and Entity-Specific Characteristics in Adenoid Cystic, Mucoepidermoid and Salivary Duct Carcinomas

SIMPLE SUMMARY: The extracellular matrix (ECM), an important factor in tumour metastasis and therapy resistance, has not been studied in salivary gland carcinomas (SGC), so far. In this retrospective study, we profiled the RNA expression of 28 ECM-related genes in 11 adenoid cystic (AdCy), 14 mucoepidermoid (MuEp) and 9 salivary duct carcinomas (SaDu). Also, we validated our results in a multimodal approach. MuEp and SaDu shared a common gene signature involving an overexpression of COL11A1. In contrast, nonhierarchical clustering revealed a more specific gene expression pattern for AdCy, characterized by overexpression of COL27A1. In situ studies at RNA level indicated that in AdCy, ECM production results from tumour cells and not from cancer-associated fibroblasts as is the case in MuEp and SaDu. For the first time, we characterized the ECM composition in SGC and identified several differentially expressed genes, which are potential therapeutic targets. ABSTRACT: The composition of the extracellular matrix (ECM) plays a pivotal role in tumour initiation, metastasis and therapy resistance. Until now, the ECM composition of salivary gland carcinomas (SGC) has not been studied. We quantitatively analysed the mRNA of 28 ECM-related genes of 34 adenoid cystic (AdCy; n = 11), mucoepidermoid (MuEp; n = 14) and salivary duct carcinomas (SaDu; n = 9). An incremental overexpression of six collagens (including COL11A1) and four glycoproteins from MuEp and SaDu suggested a common ECM alteration. Conversely, AdCy and MuEp displayed a distinct overexpression of COL27A1 and LAMB3, respectively. Nonhierarchical clustering and principal component analysis revealed a more specific pattern for AdCy with low expression of the common gene signature. In situ studies at the RNA and protein level confirmed these results and indicated that, in contrast to MuEp and SaDu, ECM production in AdCy results from tumour cells and not from cancer-associated fibroblasts (CAFs). Our findings reveal different modes of ECM production leading to common and distinct RNA signatures in SGC. Of note, an overexpression of COL27A1, as in AdCy, has not been linked to any other neoplasm so far. Here, we contribute to the dissection of the ECM composition in SGC and identified a panel of deferentially expressed genes, which could be putative targets for SGC therapy and overcoming therapeutic resistance.