Gene expression profiling in sinonasal adenocarcinoma

Abstract

BackgroundSinonasal adenocarcinomas are uncommon tumors which develop in the ethmoid sinus after exposure to wood dust. Although the etiology of these tumors is well defined, very little is known about their molecular basis and no diagnostic tool exists for their early detection in high-risk workers.MethodsTo identify genes involved in this disease, we performed gene expression profiling using cancer-dedicated microarrays, on nine matched samples of sinonasal adenocarcinomas and non-tumor sinusal tissue. Microarray results were validated by quantitative RT-PCR and immunohistochemistry on two additional sets of tumors.ResultsAmong the genes with significant differential expression we selected LGALS4, ACS5, CLU, SRI and CCT5 for further exploration. The overexpression of LGALS4, ACS5, SRI, CCT5 and the downregulation of CLU were confirmed by quantitative RT-PCR. Immunohistochemistry was performed for LGALS4 (Galectin 4), ACS5 (Acyl-CoA synthetase) and CLU (Clusterin) proteins: LGALS4 was highly up-regulated, particularly in the most differentiated tumors, while CLU was lost in all tumors. The expression of ACS5, was more heterogeneous and no correlation was observed with the tumor type.ConclusionWithin our microarray study in sinonasal adenocarcinoma we identified two proteins, LGALS4 and CLU, that were significantly differentially expressed in tumors compared to normal tissue. A further evaluation on a new set of tissues, including precancerous stages and low grade tumors, is necessary to evaluate the possibility of using them as diagnostic markers.

Identification of hub genes and pathways associated with bladder cancer based on co-expression network analysis

“…LGALS4 has been identified as one of the genes involved in numerous types of human tumor, including sinonasal adenocarcinoma tumors (34), colorectal cancer (35) and breast cancer (36). There has also been a previous report that compared expression changes at mRNA and protein levels in the rat model and identified the gene exhibiting concordant changes with LGALS4 levels in bladder tumors (37).…”

Sinonasal Carcinoma: Updated Phenotypic and Molecular Characterization

“…Tumor suppressor genes are located in regions of chromosomal losses: DCC and SMAD4 at 18q, APC at 5q, and TP53 at 17p13, [39]. Nevertheless, poorly differentiated adenocarcinomas have been reported to have a higher number of gains than well and moderately differentiated tumors, supporting the involvement of gene amplification in the process of the loss of differentiation in ITACs [41].…”

“…In a study of gene expression profiling of a small series of sinonasal adenocarcinomas, cancer-dedicated microarrays and subsequent validation via quantitative reverse transcription polymerase chain reaction and immunohistochemistry were employed [41]. Overexpression of LGALS4 (galectin 4) and the downregulation of clusterin were the two most consistent alterations observed in comparison with normal tissue [42].…”

Molecular Fingerprints of Environmental Carcinogens in Human Cancer

“…LGALS4 and CLU Head and neck (sinonasal adenocarcinoma) [96] 205 206 C. Ceccaroli et al of MT-IIA, a metal-binding protein specifically induced by cadmium. Furthermore, Zhou and associates found that exposition of human bronchial epithelial cells to cadmium chloride causes promoter hypermethylation and a decrease of mRNA and protein levels in four DNA repair genes, hMSH2, ERCC1, XRCC1, and hOGG1 [91].…”

“…To identify genes involved in sinosnasal adenocarcinomas, which are uncommon tumors developing in the ethmoid sinus after exposure to wood dust, Tripodi and associates performed gene expression profiling using cancerdedicated microarrays on nine matched samples of sinonasal adenocarcinomas and nontumor sinonasal tissue [96]. Microarray results were validated by quantitative RT-PCR and immunohistochemistry on two additional sets of tumors.…”