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Correlation analysis of mRNA expression and prognosis of hOGG1 gene polymorphism in patients with non-small cell lung cancer.

ABSTRACT: Level of mRNA expression and gene polymorphism of human 8-hydroxyguanine glycosidase 1 (hOGG1) in patients with non-small cell lung cancer (NSCLC) were investigated. A polymorphism analysis of hOGG1 gene rs1052133 locus in 182 NSCLC patients (NSCLC group) surgically treated in Xiang Yang No. 1 People's Hospital, Hubei University of Medicine from January 2008 to January 2012 and 200 healthy individuals (control group) was performed. The expression level of hOGG1 was compared between cancer tissues and adjacent tissues of NSCLC patients, and the survival rate was analyzed. The expression level of hOGG1 was significantly higher in cancer tissues than that in adjacent tissues (P<0.001). Taqman probe method was used to detect the genotypes of hOGG1 polymorphism locus rs1052133, with the genotype distribution frequencies of NSCLC group (P=0.411) and control group (P=0.354) consistent with the Hardy-Weinberg equilibrium. The proportion of C/C gene was significantly higher in NSCLC group than that in control group (P=0.008, OR=2.2, 95%, CI=1.27-4.52). The median value of the hOGG1 expression level in detection results as the boundary, NSCLC patients were divided into hOGG1 high expression group (?3.61) with 91 cases and hOGG1 low expression group (<3.61) with 91 cases. The 1-, 2- and 3-year survival rates of patients in hOGG1 low expression group were significantly higher than those in hOGG1 high expression group (P=0.007). The 3-year survival rate in hOGG1 low expression group is significantly higher than that in hOGG1 high expression group (P=0.007). The sensitivity, specificity and AUC of hOGG1 to patient survival prediction were 83.33%, 64.29%, and 0.816, respectively. In conclusion, hOGG1 is highly expressed in NSCLC tissues. Compared to S/S and S/C genotypes, the C/C gene was found to be more common in NSCLC group than in control group. Thus, hOGG1 has a high predictive value for patient survival.

SUBMITTER: Wang J

PROVIDER: S-EPMC6676738 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Correlation analysis of mRNA expression and prognosis of hOGG1 gene polymorphism in patients with non-small cell lung cancer.

Wang Jing J Wu Puzhao P

Oncology letters 20190705 3

Level of mRNA expression and gene polymorphism of human 8-hydroxyguanine glycosidase 1 (hOGG1) in patients with non-small cell lung cancer (NSCLC) were investigated. A polymorphism analysis of hOGG1 gene rs1052133 locus in 182 NSCLC patients (NSCLC group) surgically treated in Xiang Yang No. 1 People's Hospital, Hubei University of Medicine from January 2008 to January 2012 and 200 healthy individuals (control group) was performed. The expression level of hOGG1 was compared between cancer tissue ...[more]

PMID: 31402936

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Project description:Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. The nuclear factor of activated T cells (NFAT) family is implicated in tumorigenesis and progression in various types of cancer. However, little is known about their expression patterns, distinct prognostic values, and potential regulatory networks in NSCLC. In this study, we comprehensively analyzed the distinct expression and prognostic value of NFATs in NSCLC through various large databases, including the Oncomine, UCSC Xena Browser, UALCAN databases, Kaplan-Meier Plotter, cBioPortal, and Enrichr. In lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), NFAT1/2/4/5 mRNA expression levels were significantly decreased and NFAT3 mRNA expression level was significantly increased. The cBioPortal database analysis showed that the mRNA dysregulation was one of the single most important factors for NFAT alteration in LUAD and LUSC and that both LUAD and LUSC cases with the alterations in the mRNA expression of NFATs had significantly better overall survival (OS). High expression levels of NFAT1/2/4/5 were significantly associated with better OS in LUAD, whereas high NFAT3 expression led to a worse OS. Overexpression of NFAT1/2 predicted better OS in LUSC, whereas high NFAT5 expression led to a worse OS. The networks for NFATs and the 50 most frequently altered neighbor genes in LUAD and LUSC were also constructed. NFATs and genes significantly associated with NFAT mRNA expression in LUAD and LUSC were significantly enriched in the cGMP-dependent protein kinase and Wnt signaling pathways. These results showed that the NFAT family members displayed varying degrees of abnormal expressions, suggesting that NFATs may be therapeutic targets for patients with NSCLC. Aberrant expression of NFATs was found to be associated with OS in the patients with NSCLC; among NFATs, NFAT3/4 may be new biomarkers for the prognosis of LUAD. However, further studies are required to validate our findings.

Project description:Recent lung cancer studies have focused on identifying the effects of single nucleotide polymorphisms (SNPs) in candidate genes, among which DNA repair genes are increasingly being studied. Genetic variations in DNA repair genes are thought to modulate DNA repair capacity and are suggested to be related to lung cancer risk. In this study, we tried to assess reported studies of association between polymorphism of human 8-oxoguanine DNA glycosylase 1 (hOGG1) Ser326Cys and lung cancer. We conducted MEDLINE, Current Contents and Web of Science searches using "hOGG1", "lung cancer" and "polymorphism" as keywords to search for papers published (from January 1995 through August 2010). Data were combined using both a fixed effects (the inverse variance-weighted method) and a random effects (DerSimonian and Laird method) model. The Cochran Q test was used for the assessment of heterogeneity. Publication bias was assessed by both Begg's and Egger's tests. We identified 20 case-control studies in 21 different ethnic populations. As two studies were not in the Hardy-Weinberg equilibrium, 18 case-control studies in 19 different ethnic populations (7,792 cases and 9,358 controls) were included in our meta-analysis. Summary frequencies of the Cys allele among aucasians and Asians based on the random effects model were 20.9% (95% confidence interval (CI) = 18.9-22.9) and 46.1% (95% CI = 40.2-52.0), respectively. The distribution of the Cys allele was significantly different between Asians and Caucasians (P < 0.001). The Cys/Cys genotype was significantly associated with lung cancer risk in Asian populations (odds ratio = 1.27, 95% CI = 1.09-1.48) but not in Caucasian populations. This ethnic difference in lung cancer risk may be due to environmental factors such as cigarette smoking and dietary factors. Although the summary risk for developing lung cancer may not be large, lung cancer is such a common malignancy that even a small increase in risk can translate to a large number of excess lung cancer cases. As lung cancer is a multifactorial disease, further investigations of the gene-gene and gene-environment interactions on the hOGG1 polymorphism-associated lung cancer risk may help to better understand of the molecular pathogenesis of human lung cancer.

Dataset Information

Correlation analysis of mRNA expression and prognosis of hOGG1 gene polymorphism in patients with non-small cell lung cancer.

Publications

Correlation analysis of mRNA expression and prognosis of hOGG1 gene polymorphism in patients with non-small cell lung cancer.

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