Dataset Information

Association of long-chain non-coding RNA GAS5 gene polymorphisms with prostate cancer risk and prognosis in Chinese Han population.

ABSTRACT: BACKGROUND:To investigate the correlation between growth arrest-specific transcript 5 (GAS5) gene polymorphism and the risk and prognosis of prostate cancer in Chinese Han population. METHODS:Sanger sequencing was used to analyze genotypes at the rs17359906 and rs1951625 loci of the GAS5 gene in 218 prostate cancer patients and 220 healthy controls. The follow-up period was from August 2016 to August 2019, and the relationships between GAS5 gene polymorphisms at the rs17359906 and rs1951625 loci and the recurrence-free survival rate of prostate cancer patients were analyzed. RESULTS:GAS5 A-allele carriers at the rs17359906 locus were 3.44 times more likely to develop prostate cancer than G-allele carriers (95% confidence interval (CI): 2.38-4.96, P??A and rs1951625 G?>?A were associated with high plasma PSA levels. The recurrence-free survival rate of patients with prostate cancer with AA genotype at the rs17359906 locus of GAS5 (66.67%) was significantly lower than that of the GA genotype (76.47%), whereas the GG genotype was the highest (91.96%), and the difference was statistically significant (P?=?.002). The recurrence-free survival rate of patients with prostate cancer with the AA genotype at the rs1951625 locus of GAS5 (75.00%) was significantly lower than that of the GA genotype (81.82%), whereas the GG genotype was the highest (87.76%) with a statistically significant difference (P?=?.025). CONCLUSION:GAS5 rs17359906 G?>?A and rs1951625 G?>?A are significantly associated with an increased risk of prostate cancer and a reduction in three-year relapse-free survival.

SUBMITTER: Zhao L

PROVIDER: S-EPMC7478801 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Association of long-chain non-coding RNA GAS5 gene polymorphisms with prostate cancer risk and prognosis in Chinese Han population.

Zhao Lisha L Zheng Weihong W Li Chen C

Medicine 20200901 36

<h4>Background</h4>To investigate the correlation between growth arrest-specific transcript 5 (GAS5) gene polymorphism and the risk and prognosis of prostate cancer in Chinese Han population.<h4>Methods</h4>Sanger sequencing was used to analyze genotypes at the rs17359906 and rs1951625 loci of the GAS5 gene in 218 prostate cancer patients and 220 healthy controls. The follow-up period was from August 2016 to August 2019, and the relationships between GAS5 gene polymorphisms at the rs17359906 and ...[more]

PMID: 32899006

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Project description:BackgroundMalignant pleural mesothelioma (MPM) is an aggressive cancer with short overall survival. Long non-coding RNAs (lncRNA) are a class of RNAs more than 200 nucleotides long that do not code for protein and are part of the 90% of the human genome that is transcribed. Earlier experimental studies in mice showed GAS5 (growth arrest specific transcript 5) gene deletion in asbestos driven mesothelioma. GAS5 encodes for a lncRNA whose function is not well known, but it has been shown to act as glucocorticoid receptor decoy and microRNA "sponge". Our aim was to investigate the possible role of the GAS5 in the growth of MPM.MethodsPrimary MPM cultures grown in serum-free condition in 3% oxygen or MPM cell lines grown in serum-containing medium were used to investigate the modulation of GAS5 by growth arrest after inhibition of Hedgehog or PI3K/mTOR signalling. Cell cycle length was determined by EdU incorporation assay in doxycycline inducible short hairpinGAS5 clones generated from ZL55SPT cells. Gene expression was quantified by quantitative PCR. To investigate the GAS5 promoter, a 0.77 kb sequence was inserted into a pGL3 reporter vector and luciferase activity was determined after transfection into MPM cells. Localization of GAS5 lncRNA was identified by in situ hybridization. To characterize cells expressing GAS5, expression of podoplanin and Ki-67 was assessed by immunohistochemistry.ResultsGAS5 expression was lower in MPM cell lines compared to normal mesothelial cells. GAS5 was upregulated upon growth arrest induced by inhibition of Hedgehog and PI3K/mTOR signalling in in vitro MPM models. The increase in GAS5 lncRNA was accompanied by increased promoter activity. Silencing of GAS5 increased the expression of glucocorticoid responsive genes glucocorticoid inducible leucine-zipper and serum/glucocorticoid-regulated kinase-1 and shortened the length of the cell cycle. Drug induced growth arrest was associated with GAS5 accumulation in the nuclei. GAS5 was abundant in tumoral quiescent cells and it was correlated to podoplanin expression.ConclusionsThe observations that GAS5 levels modify cell proliferation in vitro, and that GAS5 expression in MPM tissue is associated with cell quiescence and podoplanin expression support a role of GAS5 in MPM biology.

Project description:BackgroundCuproptosis, an emerging form of programmed cell death, has recently been identified. However, the association between cuproptosis-related long non-coding RNA (lncRNA) signature and the prognosis in prostate carcinoma remains elusive. This study aims to develop the novel cuproptosis-related lncRNA signature in prostate cancer and explore its latent molecular function.MethodsRNA-seq data and clinical information were downloaded from the TCGA datasets. Then, cuproptosis-related gene was identified from the previous literature and further applied to screen the cuproptosis-related differentially expressed lncRNAs. Patients were randomly assigned to the training cohort or the validation cohort with a 1:1 ratio. Subsequently, the machine learning algorithms (Lasso and stepwise Cox (direction = both)) were used to construct a novel prognostic signature in the training cohorts, which was validated by the validation and the entire TCGA cohorts. The nomogram base on the lncRNA signature and several clinicopathological traits were constructed to predict the prognosis. Functional enrichment and immune analysis were performed to evaluate its potential mechanism. Furthermore, differences in the landscape of gene mutation, tumour mutational burden (TMB), microsatellite instability (MSI), drug sensitivity between both risk groups were also assessed to explicit their relationships.ResultsThe cuproptosis-related lncRNA signature was constructed based on the differentially expressed cuproptosis-related lncRNAs, including AC005790.1, AC011472.4, AC099791.2, AC144450.1, LIPE-AS1, and STPG3-AS1. Kaplan-Meier survival and ROC curves demonstrate that the prognosis signature as an independent risk indicator had excellent potential to predict the prognosis in prostate cancer. The signature was closely associated with age, T stage, N stage, and the Gleason score. Immune analysis shows that the high-risk group was in an immunosuppressive microenvironment. Additionally, the significant difference in landscape of gene mutation, tumour mutational burden, microsatellite instability, and drug sensitivity between both risk groups was observed.ConclusionsA novel cuproptosis-related lncRNA signature was constructed using machine learning algorithms to predict the prognosis of prostate cancer. It was closely with associated with several common clinical traits, immune cell infiltration, immune-related functions, immune checkpoints, gene mutation, TMB, MSI, and the drug sensitivity, which may be useful to improve the clinical outcome.

Dataset Information

Association of long-chain non-coding RNA GAS5 gene polymorphisms with prostate cancer risk and prognosis in Chinese Han population.

Publications

Association of long-chain non-coding RNA GAS5 gene polymorphisms with prostate cancer risk and prognosis in Chinese Han population.

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