外周血SEPT9基因甲基化检测在老年结直肠癌筛查中的意义
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摘要
目的探讨外周血SEPT9基因甲基化检测在老年结直肠癌筛查中的意义。方法筛查对象为1 407例军队退休干部体检者。IFOBT、TF、SEPT9基因甲基化检测三者任一结果为阳性,通知受试者行结肠镜检查。分别计算IFOBT、TF、IFOBT+TF(双联)、SEPT9基因甲基化检测和三者联合检测在老年结直肠癌筛查的性能指标。结果 1 407例军队退休干部体检者中1 369例体检者均进行了TF、IFOBT和SEPT9基因甲基化检测,至少1项结果为阳性者有176例(12.9%),其中96例(54.5%)接受了结肠镜检查,共检出9例结直肠癌和15例进展性腺瘤。使用IFOBT、TF、IFOBT+TF(双联)检测、SEPT9基因甲基化和三种方法联合检测对结直肠癌和进展期腺瘤的检出率分别为0.4%、0.1%、0.5%、1.2%、1.8%;SEPT9基因甲基化检测对结直肠癌和进展期腺瘤的检出率优于IFOBT+TF(双联)(1.2%vs 0.5%,P=0.04),但三者联合检出率较单纯SEPT9基因甲基化检测,差异无统计学意义(1.8%vs 1.2%,P=0.27),对筛查对象进行性别和年龄分层分析显示,各项检测指标男女差别不大,但SEPT9基因甲基化检测在70岁以上患者中筛查优势明显。结论 SEPT9基因甲基化是一种简单无创的结直肠癌筛查新技术,单独使用对结直肠癌和腺瘤的检出率显著高于IFOBT和TF联合检测,因此SEPT9基因甲基化检测可作为老年人结直肠癌早期筛查的首选策略。
Objective To investigate the significance of peripheral blood SEPT9 gene methylation test in screening of colorectal cancer in a senile cohort. Methods A senile cohort of 1 407 cases of retired military cadres was enrolled in the study. Colonoscopy was performed for individuals whose examination was positive of SEPT9, TF or IFOBT. Performance for SEPT9, IFOBT, IFOBT+TF(parallel), combination of the 3 methods were calculated and assessed respectively. Results There were 1 369 of 1 407 retired military cadres who had been tested by TF, IFOBT and SEPT9 gene methylation test, and there were 176 cases(12.9%) with positive examination for at least one examination. Colonoscopy was performed in 96 of the 176 individuals, 9 colorectal cancers and 15 advanced adenomas were detected. The detection rates of colorectal cancer and advanced adenoma were 0.4%, 0.1%, 0.5%, 1.2% and 1.8% by IFOBT, TF, IFOBT+TF(parallel), SEPT9 gene methylation test and combined detection rate of the 3 methods, respectively. SEPT9 gene methylation test had higher detection rate of colorectal cancer and advanced adenomas compared with IFOBT+TF(parallel)(1.2% vs 0.5%, P=0.04), but the combined detection rate of the 3 methods detection was not obviously better than SEPT9 gene methylation test(1.8% vs 1.2%, P=0.27). Stratified screening object by sex and age showed little difference between men and women, but SEPT9 gene methylation test showed better proformance in screening subjects older than 70 years old. Conclusion SEPT9 gene methylation is a simple and non-invasive new screening technology for colorectal cancer, meanwhile the detection rate of colorectal cancer and adenoma can be significantly higher than that of IFOBT+TF. Therefore, SEPT9 gene methylation test can be used as the preferred strategy of colorectal cancer screening in the elderly.
Objective To investigate the significance of peripheral blood SEPT9 gene methylation test in screening of colorectal cancer in a senile cohort. Methods A senile cohort of 1 407 cases of retired military cadres was enrolled in the study. Colonoscopy was performed for individuals whose examination was positive of SEPT9, TF or IFOBT. Performance for SEPT9, IFOBT, IFOBT+TF(parallel), combination of the 3 methods were calculated and assessed respectively. Results There were 1 369 of 1 407 retired military cadres who had been tested by TF, IFOBT and SEPT9 gene methylation test, and there were 176 cases(12.9%) with positive examination for at least one examination. Colonoscopy was performed in 96 of the 176 individuals, 9 colorectal cancers and 15 advanced adenomas were detected. The detection rates of colorectal cancer and advanced adenoma were 0.4%, 0.1%, 0.5%, 1.2% and 1.8% by IFOBT, TF, IFOBT+TF(parallel), SEPT9 gene methylation test and combined detection rate of the 3 methods, respectively. SEPT9 gene methylation test had higher detection rate of colorectal cancer and advanced adenomas compared with IFOBT+TF(parallel)(1.2% vs 0.5%, P=0.04), but the combined detection rate of the 3 methods detection was not obviously better than SEPT9 gene methylation test(1.8% vs 1.2%, P=0.27). Stratified screening object by sex and age showed little difference between men and women, but SEPT9 gene methylation test showed better proformance in screening subjects older than 70 years old. Conclusion SEPT9 gene methylation is a simple and non-invasive new screening technology for colorectal cancer, meanwhile the detection rate of colorectal cancer and adenoma can be significantly higher than that of IFOBT+TF. Therefore, SEPT9 gene methylation test can be used as the preferred strategy of colorectal cancer screening in the elderly.
引文
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[11] ADLER A,GEIGER S,KEIL A,et al.Improving compliance to colorectal cancer screening using blood and stool based tests in patients refusing screening colonoscopy in Germany [J].BMC Gastroenterol,2014,14:183.DOI:10.1186/1471-230X-14-183.
[12] TABER J M,ASPINWALL L G,HEICHMAN K A,et al.Preferences for blood-based colon cancer screening differ by race/ethnicity [J].Am J Health Behav,2014,38(3):351-361.DOI:10.5993/AJHB.38.3.4.
[13] SONG L,PENG X,LI Y,et al.The SEPT9 gene methylation assay is capable of detecting colorectal adenoma in opportunistic screening [J].Epigenomics,2017,9(5):599-610.DOI:10.2217/epi-2016-0146.
[14] GRüTZMANN R,MOLNAR B,PILARSKY C,et al.Sensitive detection of colorectal cancer in peripheral blood by septin 9 DNA methylation assay [J].PLoS One,2008,3(11):e3759.DOI:10.1371/journal.pone.0003759.
[2] REX D K,BOLAND C R,DOMINITZ J A,et al.Colorectal cancer screening:recommendations for physicians and patients from the U.S.multi-society task force on colorectal cancer [J].Gastroenterology,2017,153(1):307-323.DOI:10.1053/j.gastro.2017.05.013.
[3] PATEL S S,KILGORE M L.Cost effectiveness of colorectal cancer screening strategies [J].Cancer Control,2015,22(2):248-258.DOI:10.1177/107327481502200219.
[4] GREUTER M J,BERKHOF J,FIJNEMAN R J,et al.The potential of imaging techniques as a screening tool for colorectal cancer:a cost-effectiveness analysis [J].Br J Radiol,2016,89(1063):20150910.DOI:10.1259/bjr.20150910.
[5] JIN P,SHENG J Q,WU Z T,et al.Combined fecal transferrin test and immuno fecal occult blood test for detecting colorectal cancer and advanced adenoma in asymptomatic and symptomatic populations [J].J Cancer Sci Ther,2012,4(8):243-248.DOI:10.4172/1948-5956.1000149.
[6] TóTH K,SIPOS F,KALMáR A,et al.Detection of methylated SEPT9 in plasma is a reliable screening method for both left- and right sided colon cancers [J].PLoS One,2012,7(9):e46000.DOI:10.1371/journal.pone.0046000.
[7] JIN P,KANG Q,WANG X,et al.Performance of a second-generation methylated SEPT9 test in detecting colorectal neoplasm [J].J Gastroenterol Hepatol,2015,30(5):830-833.DOI:10.1111/jgh.12855.
[8] LAMB Y N,DHILLON S.Epi proColon?2.0 CE:A Blood-Based Screening Test for Colorectal Cancer [J].Mol Diagn Ther,2017,21(2):225-232.DOI:10.1007/s4029-017-0259-Y.
[9] ALLISON J E,SOKADA L C,LEVIN T R,et al.Screening for colorectal neoplasms with new fecal occult blood tests:update on performance characteristics [J].J Natl Cancer Inst,2007,99(19):1462-1470.DOI:10.1093/jnci/djm150.
[10] WARD D G,SUGGETT N,CHENG Y,et al.Identification of serum biomarkers for colon cancer by proteomic analysis [J].Br J Cancer,2006,94(12):1898-1905.DOI:10.1038/sj.bjc.6603188.
[11] ADLER A,GEIGER S,KEIL A,et al.Improving compliance to colorectal cancer screening using blood and stool based tests in patients refusing screening colonoscopy in Germany [J].BMC Gastroenterol,2014,14:183.DOI:10.1186/1471-230X-14-183.
[12] TABER J M,ASPINWALL L G,HEICHMAN K A,et al.Preferences for blood-based colon cancer screening differ by race/ethnicity [J].Am J Health Behav,2014,38(3):351-361.DOI:10.5993/AJHB.38.3.4.
[13] SONG L,PENG X,LI Y,et al.The SEPT9 gene methylation assay is capable of detecting colorectal adenoma in opportunistic screening [J].Epigenomics,2017,9(5):599-610.DOI:10.2217/epi-2016-0146.
[14] GRüTZMANN R,MOLNAR B,PILARSKY C,et al.Sensitive detection of colorectal cancer in peripheral blood by septin 9 DNA methylation assay [J].PLoS One,2008,3(11):e3759.DOI:10.1371/journal.pone.0003759.