Dataset Information

Genetic alteration and clinical significance of SUMOylation regulators in multiple cancer types.

ABSTRACT: The purpose of this study was to investigate the genetic variation, gene expression differences, and clinical significance of SUMOylation regulators in pan-cancers. Based on previous studies, we gained a better understanding of the biological process of SUMOylation and the status of current research. In the present study, we employed a wide range of bioinformatics methods. We used genetic variation and mRNA expression data in the Cancer Genome Atlas (TCGA) to construct a panoramic view of the single nucleotide variants, copy number variants, and gene expression changes in SUMOylation regulators in various tumors. Subsequently, we used the String website and the Cytoscape tool to construct the PPI network between these regulators. We used the GSCALite website to determine the relationship between these regulators and cancer pathways and drug sensitivity. We constructed images of co-expression between these regulators using the R programming language. Using clinical data from TCGA, we performed hazard ratio analysis for these regulators in pan-cancer. Most importantly, we used these regulators to successfully establish risk signatures related to patient prognosis in multiple tumors. Finally, in KIRC, we conducted gene-set enrichment analysis (GSEA) of the five molecules in its risk signatures. We found that these five molecules are involved in multiple cancer pathways. In short, we have comprehensively interpreted the detailed biological process of SUMOylation at the genetic level for the first time, successfully constructed multiple risk signatures, and conducted GSEA in KIRC. We believe that these findings provide credible and valuable information that is relevant for future clinical diagnoses and scientific research.

SUBMITTER: Wu G

PROVIDER: S-EPMC7592005 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetic alteration and clinical significance of SUMOylation regulators in multiple cancer types.

Wu Guangzhen G Xu Yingkun Y Ruan Ningke N Li Jianyi J Lv Qingyang Q Zhang Qi Q Chen Yougen Y Wang Qifei Q Xia Qinghua Q Li Quanlin Q

Journal of Cancer 20200930 23

The purpose of this study was to investigate the genetic variation, gene expression differences, and clinical significance of SUMOylation regulators in pan-cancers. Based on previous studies, we gained a better understanding of the biological process of SUMOylation and the status of current research. In the present study, we employed a wide range of bioinformatics methods. We used genetic variation and mRNA expression data in the Cancer Genome Atlas (TCGA) to construct a panoramic view of the si ...[more]

PMID: 33123273

Similar Datasets

Project description:Background: Many cancers share specific genetic risk factors, including both rare high-penetrance mutations and common SNPs identified through genome-wide association studies (GWAS). However, little is known about the overall shared heritability across cancers. Quantifying the extent to which two distinct cancers share genetic origin will give insights to shared biological mechanisms underlying cancer and inform design for future genetic association studies.Methods: In this study, we estimated the pair-wise genetic correlation between six cancer types (breast, colorectal, lung, ovarian, pancreatic, and prostate) using cancer-specific GWAS summary statistics data based on 66,958 case and 70,665 control subjects of European ancestry. We also estimated genetic correlations between cancers and 14 noncancer diseases and traits.Results: After adjusting for 15 pair-wise genetic correlation tests between cancers, we found significant (P < 0.003) genetic correlations between pancreatic and colorectal cancer (rg = 0.55, P = 0.003), lung and colorectal cancer (rg = 0.31, P = 0.001). We also found suggestive genetic correlations between lung and breast cancer (rg = 0.27, P = 0.009), and colorectal and breast cancer (rg = 0.22, P = 0.01). In contrast, we found no evidence that prostate cancer shared an appreciable proportion of heritability with other cancers. After adjusting for 84 tests studying genetic correlations between cancer types and other traits (Bonferroni-corrected P value: 0.0006), only the genetic correlation between lung cancer and smoking remained significant (rg = 0.41, P = 1.03 × 10-6). We also observed nominally significant genetic correlations between body mass index and all cancers except ovarian cancer.Conclusions: Our results highlight novel genetic correlations and lend support to previous observational studies that have observed links between cancers and risk factors.Impact: This study demonstrates modest genetic correlations between cancers; in particular, breast, colorectal, and lung cancer share some degree of genetic basis. Cancer Epidemiol Biomarkers Prev; 26(9); 1427-35. ©2017 AACR.

Project description:Multiple endocrine neoplasia (MEN) are clinical inherited syndromes affecting different endocrine glands. Three different patterns of MEN syndromes can occur (MEN 1, MEN 2A, and MEN 2B). MEN syndromes are very rare, affect all ages and both sexes are equally affected. MEN 1 is characterized by the neoplastic transformation of the parathyroid glands, pancreatic islets, anterior pituitary, and gastrointestinal tract. Heterozygous MEN 1 germline mutations have been detected in about 70-80% of patients with MEN 1. The mutations are scattered throughout the entire genomic sequence of the gene. MEN 1 patients are characterized by variable clinical features, thus suggesting the lack of a genotype-phenotype correlation. Therapeutical approaches are different according to the different endocrinopathies. The prognosis is generally good if adequate treatment is provided. In MEN 2 syndromes, the medullary thyroid cancer (MTC) is almost invariably present and can be associated with pheochromocytoma (PHEO) and/or multiple adenomatosis of parathyroid glands with hyperparathyroidism (PHPT). The different combination of the endocrine neoplasia gives origin to 3 syndromes: MEN 2A, MEN 2B, and FMTC. The clinical course of MTC varies considerably in the three syndromes. It is very aggressive in MEN 2B, almost indolent in the majority of patients with FMTC and with variable degrees of aggressiveness in patients with MEN 2A. Activating germline point mutations of the RET protooncogene are present in 98% of MEN 2 families. A strong genotype-phenotype correlation has been observed and a specific RET mutation may be responsible for a more or less aggressive clinical course. The treatment of choice for primary MTC is total thyroidectomy with central neck lymph nodes dissection. Nevertheless, 30% of MTC patients, especially in MEN 2B and 2A, are not cured by surgery. Recently, developed molecular therapeutics that target the RET pathway have shown very promising activity in clinical trials of patients with advanced MTC. MEN 2 prognosis is strictly dependent on the MTC aggressiveness and thus on the success of the initial treatment.

Dataset Information

Genetic alteration and clinical significance of SUMOylation regulators in multiple cancer types.

Publications

Genetic alteration and clinical significance of SUMOylation regulators in multiple cancer types.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets