Bioinformatics Centre, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China.
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150086, China.
Br J Cancer. 2014 Jul 29;111(3):525-31. doi: 10.1038/bjc.2014.347. Epub 2014 Jun 24.
Although many DNA methylation (DNAm) alterations observed in peripheral whole blood/leukocytes and serum have been considered as potential diagnostic markers for cancer, their origin and their specificity for cancer (e.g., vs inflammatory diseases) remain unclear.
From publicly available datasets, we identified changes in the methylation of blood-borne DNA for multiple cancers and inflammatory diseases. We compared the identified changes with DNAm difference between myeloid and lymphoid cells extracted from two datasets.
At least 94.7% of the differentially methylated DNA loci (DM loci) observed in peripheral whole blood/leukocytes and serum of cancer patients overlapped with DM loci that distinguish between myeloid and lymphoid cells and >99.9% of the overlapped DM loci had consistent alteration states (hyper- or hypomethylation) in cancer samples compared to normal controls with those in myeloid cells compared to lymphoid cells (binomial test, P-value <2.2 × 10(-16)). Similar results were observed for DM loci in peripheral whole blood/leukocytes in patients with rheumatoid arthritis or inflammatory bowel diseases. The direct comparison between DM loci observed in the peripheral whole blood/leukocytes of patients with inflammatory diseases and DM loci observed in the peripheral whole blood of patients with cancer showed that DM loci detected from cancer and inflammatory diseases also had significantly consistent alteration states (binomial test, P-value <2.2 × 10(-16)).
DNAm changes observed in the peripheral whole blood/leukocytes and serum of cancer patients and in the peripheral whole blood/leukocytes of inflammatory disease patients are predominantly determined by the increase of myeloid cells and the decrease of lymphoid cells under the disease conditions, in the sense that their alteration states in disease samples compared to normal controls mainly reflect the DNAm difference between myeloid and lymphoid cells. These analyses highlight the importance of comparing cancer and inflammatory disease directly for the identification of cancer-specific diagnostic biomarkers.
虽然外周全血/白细胞和血清中观察到的许多 DNA 甲基化 (DNAm) 改变被认为是癌症的潜在诊断标志物，但它们的起源及其对癌症的特异性（例如，与炎症性疾病相比）仍不清楚。
我们从公开可用的数据集确定了多种癌症和炎症性疾病患者血液源性 DNA 甲基化的变化。我们将这些变化与从两个数据集提取的骨髓细胞和淋巴样细胞之间的 DNAm 差异进行了比较。
癌症患者外周全血/白细胞和血清中观察到的差异甲基化 DNA 位点 (DM 位点) 中至少有 94.7%与区分骨髓细胞和淋巴样细胞的 DM 位点重叠，并且与正常对照相比，99.9%以上重叠的 DM 位点在癌症样本中具有一致的改变状态（超甲基化或低甲基化）与骨髓细胞相比淋巴样细胞（二项式检验，P 值<2.2×10(-16))。在类风湿关节炎或炎症性肠病患者的外周全血/白细胞中也观察到了类似的 DM 位点。在炎症性疾病患者的外周全血/白细胞中观察到的 DM 位点与癌症患者外周全血中观察到的 DM 位点之间的直接比较表明，从癌症和炎症性疾病中检测到的 DM 位点也具有明显一致的改变状态（二项式检验，P 值<2.2×10(-16))。
癌症患者外周全血/白细胞和血清以及炎症性疾病患者外周全血/白细胞中观察到的 DNAm 变化主要由疾病状态下骨髓细胞的增加和淋巴样细胞的减少决定，从病变样本与正常对照相比，其改变状态主要反映了骨髓细胞和淋巴样细胞之间的 DNAm 差异。这些分析强调了直接比较癌症和炎症性疾病以识别癌症特异性诊断生物标志物的重要性。
