Dataset Information

DNA methylation molecular subtypes for prognosis prediction in lung adenocarcinoma.

ABSTRACT:

Aims

Lung cancer is one of the main results in tumor-related mortality. Methylation differences reflect critical biological features of the etiology of LUAD and affect prognosis.

Methods

In the present study, we constructed a prediction prognostic model integrating various DNA methylation used high-throughput omics data for improved prognostic evaluation.

Results

Overall 21,120 methylation sites were identified in the training dataset. Overall, 237 promoter genes were identified by genomic annotation of 205 CpG loci. We used Akakike Information Criteria (AIC) to obtain the validity of data fitting, but to prevent overfitting. After AIC clustering, specific methylation sites of cg19224164 and cg22085335 were left. Prognostic analysis showed a significant difference among the two groups (P = 0.017). In particular, the hypermethylated group had a poor prognosis, suggesting that these methylation sites may be a marker of prognosis.

Conclusion

The model might help in the identification of unknown biomarkers in predicting patient prognosis in LUAD.

SUBMITTER: Xu D

PROVIDER: S-EPMC8991665 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

DNA methylation molecular subtypes for prognosis prediction in lung adenocarcinoma.

Xu Duoduo D Li Cheng C Zhang Youjing Y Zhang Jizhou J

BMC pulmonary medicine 20220407 1

<h4>Aims</h4>Lung cancer is one of the main results in tumor-related mortality. Methylation differences reflect critical biological features of the etiology of LUAD and affect prognosis.<h4>Methods</h4>In the present study, we constructed a prediction prognostic model integrating various DNA methylation used high-throughput omics data for improved prognostic evaluation.<h4>Results</h4>Overall 21,120 methylation sites were identified in the training dataset. Overall, 237 promoter genes were ident ...[more]

PMID: 35392867

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Project description:BackgroundCompelling lines of evidence indicate that DNA methylation of non-coding RNAs (ncRNAs) plays critical roles in various tumour progression. In addition, the differential methylation of ncRNAs can predict prognosis of patients. However, little is known about the clear relationship between DNA methylation profile of ncRNAs and the prognosis of pancreatic adenocarcinoma (PAC) patients.MethodsThe data of DNA methylation, RNA-seq, miRNA-seq and clinical features of PAC patients were collected from TCGA database. The DNA methylation profile was obtained using the Infinium HumanMethylation450 BeadChip array. LASSO regression was performed to construct two methylation-based classifiers. The risk score of methylation-based classifiers was calculated for each patient, and the accuracy of the classifiers in predicting overall survival (OS) was examined by ROC curve analysis. In addition, Cox regression models were utilized to assess whether clinical variables and the classifiers were independent prognostic factors for OS. The targets of miRNA and the genes co-expressed with lncRNA were identified with DIANA microT-CDS and the Multi-Experiment Matrix (MEM), respectively. Moreover, DAVID Bioinformatics Resources were applied to analyse the functional enrichment of these targets and co-expressed genes.ResultsA total of 4004 CpG sites of miRNA and 11,259 CpG sites of lncRNA were screened. Among these CpG sites, 8 CpG sites of miRNA and 7 CpG sites of lncRNA were found with regression coefficients. By multiplying the sum of methylation degrees of the selected CpGs with these coefficients, two methylation-based classifiers were constructed. The classifiers have shown good performance in predicting the survival rate of PAC patients at varying follow-up times. Interestingly, both of these two classifiers were predominant and independent factors for OS. Furthermore, functional enrichment analysis demonstrated that aberrantly methylated miRNAs and lncRNAs are related to calcium ion transmembrane transport and MAPK, Ras and calcium signalling pathways.ConclusionIn the present study, we identified two methylation-based classifiers of ncRNA associated with OS in PAC patients through a comprehensive analysis of miRNA and lncRNA profiles. We are the first group to demonstrate a relationship between the aberrant DNA methylation of ncRNAs and the prognosis of PAC, and this relationship would contribute to individualized PAC therapy.

Project description:BackgroundGastric cancer (GC) is a digestive system cancer with a high mortality rate globally. Previous experiences and studies have provided clinicians with ample evidence to diagnose and treat patients with reasonable therapeutic options. However, there remains a need for sensitive biomarkers that can provide clues for early diagnosis and prognosis assessment.ResultsWe found 610 independent prognosis-related 5'-cytosine-phosphate-guanine-3' (CpG) sites (P < 0.05) among 21,121 sites in the training samples. We divided the GC samples into seven clusters based on the selected 610 sites. Cluster 6 had relatively higher methylation levels and high survival rates than the other six clusters. A prognostic risk model was constructed using the significantly altered CpG sites in cluster 6 (P < 0.05). This model could distinguish high-risk GC patients from low-risk groups efficiently with the area under the receiver operating characteristic curve of 0.92. Risk assessment showed that the high-risk patients had poorer prognosis than the low-risk patients. The methylation levels of the selected sites in the established model decreased as the risk scores increased. This model had been validated in testing group and its effectiveness was confirmed. Corresponding genes of the independent prognosis-associated CpGs were identified, they were enriched in several pathways such as pathways in cancer and gastric cancer. Among all of the genes, the transcript level of transforming growth factor β2 (TGFβ2) was changed in different tumor stages, T categories, grades, and patients' survival states, and up-regulated in patients with GC compared with the normal. It was included in the pathways as pathways in cancer, hepatocellular carcinoma or gastric cancer. The methylation site located on the promoter of TGFβ2 was cg11976166.ConclusionsThis is the first study to separate GC into different molecular subtypes based on the CpG sites using a large number of samples. We constructed an effective prognosis risk model that can identify high-risk GC patients. The key CpGs sites or their corresponding genes such as TGFβ2 identified in this research can provide new clues that will enable gastroenterologists to make diagnosis or personalized prognosis assessments and better understand this disease.

Dataset Information

DNA methylation molecular subtypes for prognosis prediction in lung adenocarcinoma.

Aims

Methods

Results

Conclusion

Publications

DNA methylation molecular subtypes for prognosis prediction in lung adenocarcinoma.

Similar Datasets

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