Consistency of DM genes across different datasets for each cancer.

#<p>Each dataset was denoted by the following nomenclature: initial character of the cancer type followed by the total number of samples of the dataset.</p><p>*DM-S denotes DM genes from the shorter list;</p><p>**DM-L denotes DM genes from the longer list.</p>$<p>POG₁₂ denotes the score from the shorter list to the longer list;</p>$$<p>POG₂₁ denotes the score from the longer list to the shorter list.</p>¥<p>Consistency denotes the percentage of overlapping genes which showed the same methylation directions across the two datasets.</p

Data_Sheet_1_Efficacy and safety of EGFR-TKI combined with WBRT vs. WBRT alone in the treatment of brain metastases from NSCLC: a systematic review and meta-analysis.doc

BackgroundThe efficacy and safety of combining epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) with whole-brain radiotherapy (WBRT) for treating brain metastases in non-small cell lung cancer patients remains to be determined.MethodsA systematic search was conducted using databases including PubMed, Embase, Web of Science, Cochrane, Wanfang, and China National Knowledge Infrastructure (CNKI), aiming to identify relevant clinical studies on the treatment of brain metastases originating from non-small cell lung cancer through the combination of EGFR-TKI and WBRT. Statistical analysis was performed utilizing Stata 17.0 software, covering clinical studies published until March 1, 2023.ResultsThis analysis incorporated 23 randomized controlled trials (RCTs), involving a total of 2,025 patients. Of these, 1,011 were allocated to the group receiving both EGFR-TKI and WBRT, while 1,014 were assigned to the WBRT alone group. The findings reveal that the combination of EGFR-TKI and WBRT significantly improves the intracranial objective remission rate (RR = 1.57, 95% CI: 1.42–1.74, p ConclusionIn contrast to WBRT alone, the combination of EGFR-TKI and WBRT significantly improves intracranial response, enhancing the objective response rate, disease control rate, and 1-year survival rate in NSCLC patients with brain metastases. Moreover, aside from mild cases of rash and diarrhea, there is no statistically significant increase in the incidence of additional adverse effects. Based on the comprehensive evidence collected, the use of third-generation EGFR-TKI combined with WBRT is recommended as the preferred treatment for NSCLC patients with brain metastases, offering superior management of metastatic brain lesions.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#, CRD42023415566.</p

Consistency of DE genes across different datasets for each cancer.

<p>*DE-S denotes DE genes from the shorter list;</p><p>**DE-L denotes DE genes from the longer list.</p

Batch effects on tumour samples for nine cancer types.

<p>(a) different batches and different laboratories; (b) the same laboratory but different batches; (c) the same batch but different laboratories; (d) Hierarchical clustering the tumour samples of ovarian serous cystadenocarcinoma in batch 9 and batch 12. For a cancer type denoted in the x-axis in graph a, b or c, a box plot in the y-axis represents the percentage of probes significantly susceptible to different batch conditions. The percentage takes value ranging from 0 (no susceptible probe) to 1 (100% susceptible probes). Each box stretches from the lower hinge (defined as the 25th percentile) to the upper hinge (the 75th percentile) and the median is shown as a line across the box.</p

Concordance between differential methylation and differential expression.

§<p>Gene number denotes the number of hypermethylated (or hypomethylated) genes which were determined to be differentially expressed in the expression data.</p

The Methylation and Expression datasets of five cancer types for concordance analysis.

#<p>Each dataset is denoted by the following nomenclature: initial character of the cancer type followed by the total number of samples of the dataset; NA, not available.</p

Batch effects on DM genes of six cancer types.

<p>For each cancer type denoted in the x-axis, a box plot in the y-axis represents the consistency score defined as the proportion of DM genes with consistent methylation states among all overlapping DM gene commonly detected in both of the two groups (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029686#s2" target="_blank">‘Methods’</a> section). The consistency score takes value ranging from 0 (no consistent states) to 1 (100% consistent states). Each box stretches from the lower hinge (defined as the 25th percentile) to the upper hinge (the 75th percentile) and the median is shown as a line across the box.</p

Keratin associated protein genes hypomethylated in five cancers.

<p>Keratin associated protein genes hypomethylated in five cancers.</p

The datasets of nine cancer types for analyzing batch effects.

<p>The datasets of nine cancer types for analyzing batch effects.</p

Distinct Functional Patterns of Gene Promoter Hypomethylation and Hypermethylation in Cancer Genomes

<div><h3>Background</h3><p>Aberrant DNA methylation plays important roles in carcinogenesis. However, the functional significance of genome-wide hypermethylation and hypomethylation of gene promoters in carcinogenesis currently remain unclear.</p> <h3>Principal Findings</h3><p>Based on genome-wide methylation data for five cancer types, we showed that genes with promoter hypermethylation were highly consistent in function across different cancer types, and so were genes with promoter hypomethylation. Functions related to “developmental processes” and “regulation of biology processes” were significantly enriched with hypermethylated genes but were depleted of hypomethylated genes. In contrast, functions related to “cell killing” and “response to stimulus”, including immune and inflammatory response, were associated with an enrichment of hypomethylated genes and depletion of hypermethylated genes. We also observed that some families of cytokines secreted by immune cells, such as IL10 family cytokines and chemokines, tended to be hypomethylated in various cancer types. These results provide new hints for understanding the distinct functional roles of genome-wide hypermethylation and hypomethylation of gene promoters in carcinogenesis.</p> <h3>Conclusions</h3><p>Genes with promoter hypermethylation and hypomethylation are highly consistent in function across different cancer types, respectively, but these two groups of genes tend to be enriched in different functions associated with cancer. Especially, we speculate that hypomethylation of gene promoters may play roles in inducing immunity and inflammation disorders in precancerous conditions, which may provide hints for improving epigenetic therapy and immunotherapy of cancer.</p> </div