Dataset Information

A cellular and bioinformatics analysis of the SENP1 SUMO isopeptidase in pancreatic cancer.

ABSTRACT: Sumoylation is an important post-translational modification that involves the conjugation of the Small Ubiquitin-related Modifier (SUMO) onto target proteins. This modification is reversed through the catalytic activity of SUMO isopeptidases, known as SENPs. One of these SENPs, SENP1, was reported to be overexpressed in human pancreatic cancer cells and patient tissues. Since elevated SENP1 expression levels can be used as a prognostic marker for a subset of cancers, we set out to further explore the overexpression of SENP1 in pancreatic cancer. We found that SENP1 protein levels were not significantly different between pancreatic cancer and normal pancreas-derived cell lines. To evaluate SENP1 expression in patient samples, we analyzed large publicly available datasets and found that SENP1 mRNA levels were significantly lower in pancreatic cancer tissue as compared to normal pancreas tissue samples. Furthermore, we found that the SENP1 gene is amplified in less than 1% of sequenced pancreatic cancer patient samples and that expression levels have no association with patient survival. Based on our analysis, we conclude that SENP1 is not overexpressed in pancreatic cancer and is therefore not likely to be an effective biomarker for this disease. Through this work, we also outline a simple but powerful bioinformatics workflow for the assessment of mRNA expression levels, genomic alterations and survival analysis for putative biomarkers for common human cancers.

SUBMITTER: Bouchard DM

PROVIDER: S-EPMC6776818 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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A cellular and bioinformatics analysis of the SENP1 SUMO isopeptidase in pancreatic cancer.

Bouchard Danielle M DM Matunis Michael J MJ

Journal of gastrointestinal oncology 20191001 5

Sumoylation is an important post-translational modification that involves the conjugation of the Small Ubiquitin-related Modifier (SUMO) onto target proteins. This modification is reversed through the catalytic activity of SUMO isopeptidases, known as SENPs. One of these SENPs, SENP1, was reported to be overexpressed in human pancreatic cancer cells and patient tissues. Since elevated SENP1 expression levels can be used as a prognostic marker for a subset of cancers, we set out to further explor ...[more]

PMID: 31602319

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Project description:SENP proteases take part in post-translational modification of proteins known as sumoylation. They catalyze three distinct processes during sumoylation: processing of SUMO protein, deconjugation of SUMO from the target protein, and chain editing which mentions to the dismantling of SUMO chain. Many proteins that are involved in the basic processes of cells, such as regulation of transcription, DNA repair or cell cycle control, are sumoylated. The aim of these studies was to investigate an association between polymorphic variants (SNPs) of the SENP1 gene (c.1691 + 36C > T, rs12297820) and SENP2 gene (c.902C > A, p.Thr301Lys, rs6762208) and a risk of breast cancer occurrence. We performed a case-control study in 324 breast cancer cases and 335 controls using PCR-RLFP. In the case of the SENP1 gene polymorphism we did not find any association between this polymorphism and breast cancer risk. In the case of SENP2 gene polymorphism we observed higher risk of breast cancer for carriers of the A allele (OR =1.33; 95 % CI 1.04-1.69). Our analysis also showed the genotype C/C (OR =0.67, 95 % CI 0.48-0.93) and the allele C (OR =0.75, 95 % CI 0.59-0.69) of this polymorphism decrease a risk of breast cancer. We also checked the distribution of genotypes and frequency of alleles of the SENP1 and SENP2 genes polymorphisms in groups of patients with different hormone receptor status, patients with positive and negative lymph node status and patients with different tumor grade. Odds ratio analysis showed a higher risk of metastases in women with the genotype C/C (OR =2.07, 95 % CI 1.06-4.05) and allele C (OR =2.10 95 % CI 1.10-4.01) of the c.1691 + 36C > T SENP1 gene polymorphism. Moreover, we observed reduced risk in women with the allele T (OR =0.48, 95 % CI 0.25-0.91) in this polymorphic site. In the case of SENP2 gene polymorphism we observed that the A/A genotype correlated with the lack of estrogen receptor (OR =1.94, 95 % CI 1.04-3.62). Our results suggest that the variability of the SENP1 and SENP2 genes may play a role in breast cancer occurrence. Further studies are needed to clarify their biological functions in breast cancer.

Project description:BackgroundPancreatic cancer, particularly pancreatic ductal adenocarcinoma (PDA), is an aggressive malignancy associated with a low 5-year survival rate. Poor outcomes associated with PDA are attributable to late detection and inoperability. Most patients with PDA are diagnosed with locally advanced and metastatic disease. Such cases are primarily treated with chemotherapy and radiotherapy. Because of the lack of effective molecular targets, early diagnosis and successful therapies are limited. The purpose of this study was to screen key candidate genes for PDA using a bioinformatic approach and to research their potential functional, pathway mechanisms associated with PDA progression. It may help to understand the role of associated genes in the development and progression of PDA and identify relevant molecular markers with value for early diagnosis and targeted therapy.Materials and methodsTo identify novel genes associated with carcinogenesis and progression of PDA, we analyzed the microarray datasets GSE62165, GSE125158, and GSE71989 from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified, and the Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A protein-protein interaction (PPI) network was constructed using STRING, and module analysis was performed using Cytoscape. Gene Expression Profiling Interactive Analysis (GEPIA) was used to evaluate the differential expression of hub genes in patients with PDA. In addition, we verified the expression of these genes in PDA cell lines and normal pancreatic epithelial cells.ResultsA total of 202 DEGs were identified and these were found to be enriched for various functions and pathways, including cell adhesion, leukocyte migration, extracellular matrix organization, extracellular region, collagen trimer, membrane raft, fibronectin-binding, integrin binding, protein digestion, and absorption, and focal adhesion. Among these DEGs, 12 hub genes with high degrees of connectivity were selected. Survival analysis showed that the hub genes (HMMR, CEP55, CDK1, UHRF1, ASPM, RAD51AP1, DLGAP5, KIF11, SHCBP1, PBK, and HMGB2) may be involved in the tumorigenesis and development of PDA, highlighting their potential as diagnostic and therapeutic factors in PDA.ConclusionsIn summary, the DEGs and hub genes identified in the present study not only contribute to a better understanding of the molecular mechanisms underlying the carcinogenesis and progression of PDA but may also serve as potential new biomarkers and targets for PDA.

Dataset Information

A cellular and bioinformatics analysis of the SENP1 SUMO isopeptidase in pancreatic cancer.

Publications

A cellular and bioinformatics analysis of the SENP1 SUMO isopeptidase in pancreatic cancer.

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