Laboratory of Theoretical Biophysics, School of Physical Science and Technology, Inner Mongolia University, Hohhot, 010021, China.
Laboratory of Theoretical Biophysics, School of Physical Science and Technology, Inner Mongolia University, Hohhot, 010021, China; The State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot, 010070, China.
Comput Biol Med. 2024 Feb;169:107884. doi: 10.1016/j.compbiomed.2023.107884. Epub 2023 Dec 22.
Overall cancer hypomethylation had been identified in the past, but it is not clear exactly which hypomethylation site is the more important for the occurrence of cancer. To identify key hypomethylation sites, we studied the effect of hypomethylation in twelve regions on gene expression in colon adenocarcinoma (COAD). The key DNA methylation sites of cg18949415, cg22193385 and important genes of C6orf223, KRT7 were found by constructing a prognostic model, survival analysis and random combination prediction a series of in-depth systematic calculations and analyses, and the results were validated by GEO database, immune microenvironment, drug and functional enrichment analysis. Based on the expression values of C6orf223, KRT7 genes and the DNA methylation values of cg18949415, cg22193385 sites, the least diversity increment algorithm were used to predict COAD and normal sample. The 100 % reliability and 97.12 % correctness of predicting tumor samples were obtained in jackknife test. Moreover, we found that C6orf223 gene, cg18949415 site play a more important role than KRT7 gene, cg22193385 site in COAD. In addition, we investigate the impact of key methylation sites on three-dimensional chromatin structure. Our results will be help for experimental studies and may be an epigenetic biomarker for COAD.
过去已经确定了整体癌症低甲基化，但尚不清楚哪个低甲基化位点对癌症的发生更为重要。为了确定关键的低甲基化位点，我们研究了十二种区域的低甲基化对结肠腺癌（COAD）基因表达的影响。通过构建预后模型、生存分析和随机组合预测等一系列深入的系统计算和分析，找到了 cg18949415、cg22193385 等关键 DNA 甲基化位点和 C6orf223、KRT7 等重要基因。并通过 GEO 数据库、免疫微环境、药物和功能富集分析进行了验证。基于 C6orf223、KRT7 基因的表达值和 cg18949415、cg22193385 位点的 DNA 甲基化值，采用最小差异增量算法预测 COAD 和正常样本，在 jackknife 检验中获得了 100%的可靠性和 97.12%的正确性。此外，我们发现 C6orf223 基因、cg18949415 位点在 COAD 中比 KRT7 基因、cg22193385 位点发挥更重要的作用。此外，我们还研究了关键甲基化位点对三维染色质结构的影响。我们的研究结果将有助于实验研究，并可能成为 COAD 的表观遗传生物标志物。
