检测结直肠癌、乳腺癌和前列腺癌患者血液和组织中的高甲基化 BCAT1 和 IKZF1 DNA。
Detection of hypermethylated BCAT1 and IKZF1 DNA in blood and tissues of colorectal, breast and prostate cancer patients.
机构信息
Cancer Research, Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University of South Australia, Bedford Park, South Australia, Australia.
Bowel Health Service, Flinders Medical Centre, Bedford Park, South Australia, Australia.
出版信息
Cancer Biomark. 2022;34(3):493-503. doi: 10.3233/CBM-210399.
BACKGROUND
Detection of circulating cell-free DNA (ccfDNA) methylated in BCAT1 and IKZF1 is sensitive for detection of colorectal cancer (CRC), but it is not known if these biomarkers are present in other common adenocarcinomas.
OBJECTIVE
Compare methylation levels of BCAT1 and IKZF1 in tissue and plasma from breast, prostate, and colorectal cancer patients.
METHODS
Blood was collected from 290 CRC, 32 breast and 101 prostate cancer patients, and 606 cancer-free controls. Tumor and matched normal tissues were collected at surgery: 26 breast, 9 prostate and 15 CRC. DNA methylation in BCAT1 and IKZF1 was measured in blood and tissues.
RESULTS
Either biomarker was detected in blood from 175/290 (60.3%) of CRC patients. The detection rate was higher than that measured in controls (48/606 (8.1%), OR = 18.2, 95%CI: 11.1-29.0). The test positivity rates in breast and prostate cancer patients were 9.4% (3/32) and 6.9% (7/101), respectively, and not significantly different to that measured in gender-matched controls (8.0% (33/382) females (OR = 0.84, 95%CI: 0.23-3.1) and 7.6% (26/318) males (OR = 0.86, 95%CI: 0.65-2.1). In tumor and non-neoplastic tissues, 93.5% (14/15) of CRC tumors were methylated in BCAT1 and/or IKZF1 (p< 0.004). Only 11.5% (3/26) and 44.4% (4/9) (p= 0.083) of breast and prostate tumors were hypermethylated in these two genes.
CONCLUSIONS
Detection of circulating DNA methylated in BCAT1 and IKZF1 is sensitive and specific for CRC but not breast or prostate cancer.
背景
检测血液中循环游离 DNA（ccfDNA）中 BCAT1 和 IKZF1 的甲基化情况对结直肠癌（CRC）的检测具有较高的敏感性，但目前尚不清楚这些生物标志物是否存在于其他常见的腺癌中。
目的
比较组织和血浆中 BCAT1 和 IKZF1 在乳腺癌、前列腺癌和结直肠癌患者中的甲基化水平。
方法
收集了 290 例 CRC、32 例乳腺癌和 101 例前列腺癌患者以及 606 例无癌症对照者的血液。在手术时采集了肿瘤和匹配的正常组织：26 例乳腺癌、9 例前列腺癌和 15 例 CRC。在血液和组织中测量了 BCAT1 和 IKZF1 的 DNA 甲基化。
结果
在 290 例 CRC 患者中有 175/290（60.3%）例患者的血液中检测到了这两种生物标志物。检测率高于对照组（606 例中的 48/606（8.1%），OR=18.2，95%CI：11.1-29.0）。在乳腺癌和前列腺癌患者中，阳性检出率分别为 9.4%（3/32）和 6.9%（7/101），与性别匹配的对照组相比无显著差异（32 例女性中的 8.0%（33/382）（OR=0.84，95%CI：0.23-3.1）和 318 例男性中的 7.6%（26/318）（OR=0.86，95%CI：0.65-2.1））。在肿瘤和非肿瘤组织中，15 例 CRC 肿瘤中有 93.5%（14/15）在 BCAT1 和/或 IKZF1 中发生了甲基化（p<0.004）。在这两个基因中，仅有 11.5%（3/26）和 44.4%（4/9）（p=0.083）的乳腺癌和前列腺癌肿瘤发生了过度甲基化。
结论
检测血液中循环游离 DNA 中 BCAT1 和 IKZF1 的甲基化情况对 CRC 具有较高的敏感性和特异性，但对乳腺癌或前列腺癌无此作用。
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