RESUMO
BACKGROUND: Dysregulation of glycogene expression in cancer can lead to aberrant glycan expression, which can promote tumorigenesis. Cervical cancer (CC) displays an increased expression of glycogenes involved in sialylation and sialylated glycans. Here, we show a comprehensive analysis of glycogene expression in CC to identify glycogene expression signatures and the possible glycosylation pathways altered. METHODS: First, we performed a microarray expression assay to compare glycogene expression changes between normal and cervical cancer tissues. Second, we used 401 glycogenes to analyze glycogene expression in adenocarcinoma and squamous carcinoma from RNA-seq data at the cBioPortal for Cancer Genomics. RESULTS: The analysis of the microarray expression assay indicated that CC displayed an increase in glycogenes related to GPI-anchored biosynthesis and a decrease in genes associated with chondroitin and dermatan sulfate with respect to normal tissue. Also, the glycogene analysis of CC samples by the RNA-seq showed that the glycogenes involved in the chondroitin and dermatan sulfate pathway were downregulated. Interestingly the adenocarcinoma tumors displayed a unique glycogene expression signature compared to squamous cancer that shows heterogeneous glycogene expression divided into six types. Squamous carcinoma type 5 (SCC-5) showed increased expression of genes implicated in keratan and heparan sulfate synthesis, glycosaminoglycan degradation, ganglio, and globo glycosphingolipid synthesis was related to poorly differentiated tumors and poor survival. Squamous carcinoma type 6 (SCC-6) displayed an increased expression of genes involved in chondroitin/dermatan sulfate synthesis and lacto and neolacto glycosphingolipid synthesis and was associated with nonkeratinizing squamous cancer and good survival. In summary, our study showed that CC tumors are not a uniform entity, and their glycome signatures could be related to different clinicopathological characteristics.
RESUMO
Sialyltransferase gene expression is altered in several cancers, including examples in the cervix. Transcriptional regulation of the responsible genes depends on different promoters. We aimed to determine the association of single-nucleotide polymorphisms in the B3 promoter of the ST3GAL4 gene and the P1 promoter of the ST6GAL1 gene with cervical premalignant lesions or cervical cancer. A blood sample and/or cervical scrapes were obtained from 104 women with normal cytology, 154 with premalignant lesions and 100 with cervical cancer. We also included 119 blood samples of random donors. The polymorphisms were identified by sequencing from PCR products. For the B3 promoter, a fragment of 506 bp (from nucleotide -408 to +98) was analyzed, and for the P1 promoter a 490 bp (-326 to +164) fragment. The polymorphism analysis showed that at SNP rs10893506, genotypes CC and CT of the ST3GAL4 B3 promoter were associated with the presence of premalignant lesions (OR=2.89; 95%CI 1.72-4.85) and cervical cancer (OR=2.23; 95%CI 1.27-3.91). We detected only one allele of each polymorphism in the ST6GAL1 P1 promoter. We did not detect any genetic variability in the P1 promoter region in our study population. Our results suggest that the rs10893506 polymorphism -22C/T may increase susceptibility to premalignant and malignant lesions of the cervix.