Expression Profiling of Extracellular Matrix Genes Reveals Global and Entity-Specific Characteristics in Adenoid Cystic, Mucoepidermoid and Salivary Duct Carcinomas.
Christoph AroltMoritz MeyerFranziska HoffmannSvenja Wagener-RyczekDavid SchwarzLisa NachtsheimDirk BeutnerMargarete OdenthalOrlando Guntinas-LichiusReinhard BuettnerFerdinand von EggelingJens Peter KlußmannAlexander QuaasPublished in: Cancers (2020)
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.
Keyphrases
- extracellular matrix
- genome wide
- genome wide identification
- cell proliferation
- high grade
- transcription factor
- single cell
- poor prognosis
- binding protein
- magnetic resonance
- copy number
- gene expression
- stem cells
- magnetic resonance imaging
- small molecule
- computed tomography
- contrast enhanced
- protein protein
- solid state