Dataset Information

Hypermethylation of MDFI promoter with NSCLC is specific for females, non-smokers and people younger than 65.

ABSTRACT: Non-small cell lung carcinoma (NSCLC) is a major subtype of lung cancer. Aberrant DNA methylation has been frequently observed in NSCLC. The aim of the present study was to investigate the role of MyoD family inhibitor (MDFI) methylation in NSCLC. Formalin-fixed paraffin-embedded tumor tissues and adjacent non-cancerous tissues were collected from a total of 111 patients with NSCLC. A methylation assay was performed using the quantitative methylation-specific polymerase chain reaction method. The percentage of methylated reference was used to represent the methylation level of the MDFI promoter. Data mining of a dataset from The Cancer Genome Atlas (TCGA) demonstrated that MDFI promoter methylation levels were significantly increased in 830 tumor tissues compared with 75 non-tumor tissues (P=0.012). However, the results on tissues obtained in the present study indicated that the MDFI promoter methylation levels in tumor tissues were not significantly different compared with those in the adjacent non-tumor tissues (P=0.159). Subsequent breakdown analysis identified that higher MDFI promoter methylation levels were significantly associated with NSCLC in females (P=0.031), but not in males (P=0.832). Age-based subgroup analysis demonstrated that higher MDFI promoter methylation levels were significantly associated with NSCLC in younger patients (?65 years; P=0.003), but not in older patients (P=0.327). In addition, the association of MDFI methylation with NSCLC was significant in non-smokers (P=0.014), but not in smokers (P=0.832). Similar results also have been determined from subgroup analysis of the TCGA datasets. The Gene Expression Omnibus database indicated MDFI expression restoration in partial lung cancer cell lines (H1299 and Hotz) following demethylation treatment. However, it was identified that MDFI promoter hypermethylation was not significantly associated with prognosis of NSCLC (P>0.05). In conclusion, the present study indicated that the association of higher methylation of the MDFI promoter with NSCLC may be specific to females, non-smokers and people aged ?65.

SUBMITTER: Ma H

PROVIDER: S-EPMC5958687 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Hypermethylation of <i>MDFI</i> promoter with NSCLC is specific for females, non-smokers and people younger than 65.

Ma Hongying H Chen Xiaoying X Hu Haochang H Li Bin B Ying Xiuru X Zhou Cong C Zhong Jie J Zhao Guofang G Duan Shiwei S

Oncology letters 20180418 6

Non-small cell lung carcinoma (NSCLC) is a major subtype of lung cancer. Aberrant DNA methylation has been frequently observed in NSCLC. The aim of the present study was to investigate the role of MyoD family inhibitor (<i>MDFI</i>) methylation in NSCLC. Formalin-fixed paraffin-embedded tumor tissues and adjacent non-cancerous tissues were collected from a total of 111 patients with NSCLC. A methylation assay was performed using the quantitative methylation-specific polymerase chain reaction met ...[more]

PMID: 29805634

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Project description:BackgroundThe triglyceride-glucose index (TGI), a reliable surrogate indicator of insulin resistance (IR), has been proven to be a predictor of the incidence of ischemic stroke. The role of TGI in predicting the outcomes of stroke patients remains controversial. Susceptibility to IR-related diseases varies among patients of different ages. The study aims to evaluate the predictive value of TGI levels on clinical outcomes of patients with ischemic stroke of different ages.MethodThis was a retrospective cohort study including patients with ischemic stroke in the Department of Neurology at West China Hospital. TGI was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. The patients were subdivided into 3 tertiles according to TGI levels. Multivariate logistic regression analyses were conducted to estimate the association between TGI levels and post-stroke outcomes among the whole patients, younger patients (<65), and older patients (>=65). The outcomes included death and unfavorable functional outcome (modified Rankin scale score 3-6) at 3 and 12 months after stroke.ResultsA total of 3,704 patients (men, 65.08%, mean age, 61.44 ± 14.15; women 34.92%, mean age, 65.70 ± 13.69) were enrolled in this study. TGI levels were not associated with 3 month or 12 month death in the whole patients. Patients with higher TGI levels (T2 and T3) had a higher risk of 3 month death than those had lower TGI levels (T1) in the younger group (T2 vs. T1: OR 2.64, 95% CI 1.03-6.79, p = 0.043; T3 vs. T1: OR 2.69, 95% CI 1.00-7.10, p = 0.049) but not in the older group. Additionally, Kaplan-Meier estimate analysis illustrated that the 12 month death risk was significantly higher in the group with the highest TGI among younger patients (p for log-rank test = 0.028) but not among older patients. There was an interactive effect between TGI and age on 3 month death (p for interaction = 0.013) and 12 month death (p for interaction = 0.027). However, TGI was not associated with unfavorable functional outcome at 3 month or 12 month after stroke.ConclusionElevated TGI independently predicts death at 3 months and 12 months in patients under 65 with ischemic stroke. Regulating TGI is expected to be an approach to enhance prognosis in young individuals affected by ischemic stroke.

Project description:BackgroundLeucine-rich repeat C4 protein (LRRC4) is a new member of the leucine-rich repeat (LRR) superfamily. It is not only a brain-specific gene but also a novel candidate for tumor suppression. LRRC4 inactivation is commonly found in glioma cell lines and primary glioma biopsies. However, little is known about the mechanism controlling LRRC4 expression. In a previous study, we did not find any genetic alteration in LRRC4 in primary glioma, which led us to explore an alternative mechanism underlying this phenomenon.MethodsIn the present paper, we cloned the LRRC4 promoter with characteristics of a CpG island by luciferase reporter assay. Then, the CpG methylation status around the LRRC4 promoter region in glioma cell lines and primary gliomas was examined by methylation-specific PCR and bisulfite DNA sequencing. In order to demonstrate a functional association between LRRC4 promoter methylation and its gene inactivation, we performed DNA demethylation analysis with two human glioma cell lines using methylation-specific PCR and RT-PCR.ResultsThe sequence spanning positions -835 to -293 relative to the translation start site was identified as the LRRC4 promoter; this sequence is a TATA- and CAAT- less, high GC content region. It was found that LRRC4 promoter activity is strongly suppressed after treatment with SssI methylase in vitro. Furthermore, LRRC4 promoter methylation was observed by methylation-specific PCR in two glioma cell lines and all 30 primary glioma specimens, but not in normal brain tissue. Bisulfite DNA sequencing showed that most of the CpG sites were located around the LRRC4 promoter methylated in glioma cells and tissues, but not in normal brain tissue. In addition, the methylase inhibitor 5-Aza-2'-deoxycytidine could induce LRRC4 mRNA expression and LRRC4 promoter partial demethylation in SF126 and SF767 glioma cells.ConclusionMethylation-mediated inactivation of LRRC4 is a frequent and glioma-specific event, and it may be a potential biomarker for diagnosis or prognosis, or serve as a therapeutic target.

Dataset Information

Hypermethylation of MDFI promoter with NSCLC is specific for females, non-smokers and people younger than 65.

Publications

Hypermethylation of <i>MDFI</i> promoter with NSCLC is specific for females, non-smokers and people younger than 65.

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