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

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.

Collagen Type XI Alpha 1 (COL11A1): A Novel Biomarker and a Key Player in Cancer

“…COL11A1 expression is absent in benign pathological conditions involving desmoplasia such as hyperplasia, fibrosis, cirrhosis, pancreatitis and inflammatory bowel disease or premalignant lesions [ 2 , 13 ]. Interestingly, in invasive carcinomas, high expression of COL11A1 is detected in the stroma of breast, colorectal, esophagus, glioma, gastric, lung, ovarian, pancreatic and salivary gland cancers [ 14 , 24 , 25 , 26 , 27 , 29 , 33 , 47 , 48 , 49 , 50 , 51 , 52 ] ( Table 1 , Figure 1 ). Moreover, in these cancers, the expression of COL11A1 positively correlates with progression and lymph node metastasis.…”

Transcriptomic meta-analysis of non-Hodgkin’s B-cell lymphomas reveals reliance on pathways associated with the extracellular matrix

“…Collagen type XXVII alpha 1 chain (COL27A1) having significant changes among its expressed splice variants in BCNHL is interesting since it was recently reported as being overexpressed in adenoid cystic carcinoma (52). Like COL1A1, COL27A1 is a member of the upregulated Extracellular matrix organization and Collagen formation pathways, suggesting that COL27A1 could play a role in BCNHL extravasation.…”

Trophoblast Cell Surface Antigen 2 (Trop-2) Protein is Highly Expressed in Salivary Gland Carcinomas and Represents a Potential Therapeutic Target

“…Three exemplary cases with high expression, two with moderate, three with weak and two with negative expression of Trop-2 in IHC were analyzed. Sample preparation including deparaffinization, antigen retrieval, tryptic digestion and matrix application was performed according to a previously published study [30]. MALDI-MS Imaging measurements were performed on ultrafleXtreme mass spectrometer (Bruker Daltonik GmbH, Germany).…”