外周血SEPT9基因甲基化检测在结直肠癌筛查及术后随访中的意义分析
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摘要
目的探讨外周血SEPT9基因甲基化检测在结直肠癌筛查及随访中的应用。方法回顾性分析2014年10月至2015年12月接受结直肠癌筛查人群共计783例,其中确诊结直肠癌患者72例,非结直肠癌患者711例。对所有纳入患者进行外周血SEPT9甲基化检测和病理检查。以病理诊断为金标准,采用ROC曲线分析SEPT9阳性对结直肠癌的诊断价值,术后随访1年,观察外周血SEPT9基因甲基化和患者生存情况的关系。应用SPSS 23. 0软件进行统计学分析,性别、年龄段、病变位置、TNM分期等资料以[例(%)]表示,比较采用卡方检验,以P <0. 05为差异有统计学意义。结果结直肠癌患者SEPT9基因甲基化(70. 8%)显著高于非结直肠癌患者(13. 5%); SEPT9基因甲基化在TNM分期Ⅰ期、Ⅱ期、Ⅲ期及Ⅳ期结直肠癌患者的阳性率依次为:47. 4%、69. 2%、88. 9%、88. 9%。ROC曲线分析显示,SEPT9的AUC=0. 787,高于CA125和CA199(P <0. 05),其诊断结直肠癌的灵敏度为86. 5%,特异度为70. 8%。术后随访1年发现,88. 2%的SEPT9基因甲基化阳性患者在结直肠癌根治术后转为阴性,与SEPT9甲基化转阴性的患者相比较,SEPT9甲基化未转为阴性的患者预后较差。结论 SEPT9基因甲基化检测可能作为评估结直肠癌风险和预后的一项重要检测指标。
Objective To study the analysis of SEPT9 gene methylation in diagnosis and follow-up of colorectal cancer. Methods The clinical data of 783 cases of colorectal cancer screening in our hospital from October 2014 to December 2015 were analyzed. There were 72 patients diagnosed with colorectal cancer,711 cases were excluded colorectal cancer. In there,all patients were performed by peripheral blood SEPT9 methylation detection and pathological examination. Pathological diagnosis was used as gold standard,with the ROC curve,the diagnostic value of SEPT9 positive for colorectal cancer was evaluated. After 1 years of follow-up,the SEPT9 gene methylation and the survival of the patients were observed. Statistical analysis were performed by using SPSS 23. 0 software,the classification data such as sex,age,location of lesion,TNM stage and et al were presented as n( %),and examined by using Chi square test. A P < 0. 05 was considered as significant difference. Results The level of SEPT9 gene methylation of colorectal cancer patients was significant higher than non-colorectal cancer patients. The positive rate of SEPT9 gene methylation of colorectal cancer patients in stage Ⅰ,stage Ⅱ,stage Ⅲ and Ⅳ was 47. 4%,69. 2%,88. 89%,88. 9% respectivly. ROC curve analysis showed that the SEPT9 was higher than that of CA125 and CA199 curve( P < 0. 05),the sensitivity and specificity of the diagnosis of colorectal cancer was 86. 5%and 70. 8%. After 1 year of follow-up,88. 2% of positive SEPT9 gene methylation patients turned to negative after colorectal cancer surgery,compared with this patients,the prognosis of patients whose SEPT9 methylation had not turned to negative had a poor prognosis. Conclusion SEPT9 gene methylation could be used as an important test indicator for the risk and prognosis of colorectal cancer.
Objective To study the analysis of SEPT9 gene methylation in diagnosis and follow-up of colorectal cancer. Methods The clinical data of 783 cases of colorectal cancer screening in our hospital from October 2014 to December 2015 were analyzed. There were 72 patients diagnosed with colorectal cancer,711 cases were excluded colorectal cancer. In there,all patients were performed by peripheral blood SEPT9 methylation detection and pathological examination. Pathological diagnosis was used as gold standard,with the ROC curve,the diagnostic value of SEPT9 positive for colorectal cancer was evaluated. After 1 years of follow-up,the SEPT9 gene methylation and the survival of the patients were observed. Statistical analysis were performed by using SPSS 23. 0 software,the classification data such as sex,age,location of lesion,TNM stage and et al were presented as n( %),and examined by using Chi square test. A P < 0. 05 was considered as significant difference. Results The level of SEPT9 gene methylation of colorectal cancer patients was significant higher than non-colorectal cancer patients. The positive rate of SEPT9 gene methylation of colorectal cancer patients in stage Ⅰ,stage Ⅱ,stage Ⅲ and Ⅳ was 47. 4%,69. 2%,88. 89%,88. 9% respectivly. ROC curve analysis showed that the SEPT9 was higher than that of CA125 and CA199 curve( P < 0. 05),the sensitivity and specificity of the diagnosis of colorectal cancer was 86. 5%and 70. 8%. After 1 year of follow-up,88. 2% of positive SEPT9 gene methylation patients turned to negative after colorectal cancer surgery,compared with this patients,the prognosis of patients whose SEPT9 methylation had not turned to negative had a poor prognosis. Conclusion SEPT9 gene methylation could be used as an important test indicator for the risk and prognosis of colorectal cancer.
引文
[1]陈功,万德森.结直肠癌防治研究最新进展[J].广东医学,2016,37(22):3323-3328.
[2]刘茉,王亚东,王贵齐,等.基于慢病管理的结直肠癌筛查模式初探[J].中华疾病控制杂志,2015,19(5):524-527.
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[5] Molnár B,Tóth K,Barták BK,et al. Plasma methylated septin 9:a colorectal cancer screening marker[J]. Expert Rev Mol Diagn,2015,15(2):171-184.
[6] Song L,Li Y. Chapter Four-SEPT9:A Specific Circulating Biomarker for Colorectal Cancer[J]. Adv Clin Chem,2015,72(7):171-204.
[7] Spiliotis ET,Kinoshita M,Nelson WJ. A mitotic septin scaffold required for Mammalian chromosome congression and segregation[J]. Science,2005,307(5716):1781-1785.
[8] Li Y,Song L,Gong Y,et al. Detection of colorectal cancer by DNA methylation biomarker SEPT9:past,present and future[J]. Biomark Med,2014,8(5):755-769.
[9] Payne SR. From discovery to the clinic:the novel DNA methylation biomarker(m)SEPT9 for the detection of colorectal cancer in blood[J]. Epigenomics,2016,2(4):575-585.
[10] Lofton-Day C,Model F,Devos T,et al. DNA methylation biomarkers for blood-based colorectal cancer screening[J]. Clin Chem,2008,54(2):414-423.
[11] 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.
[12] Wasserkort R,Kalmar A,Valcz G,et al. Aberrant septin 9 DNA methylation in colorectal cancer is restricted to a single CpG island[J]. BMC Cancer,2013,13(1):398-398.
[13] Yan S,Liu Z,Yu S,et al. Diagnostic Value of Methylated SEPT9for Colorectal Cancer Screening:A Meta-Analysis[J]. Med Sci Monit,2016,22(9):3409-3418.
[14] Kang Q,Jin P,Yang L,et al. Significance of SEPT9 gene methylation detection of plasma circulation DNA in colorectal cancer screening[J]. Zhonghua Yi Xue Za Zhi,2014,94(48):3839-3841.
[15]贺娜,吴开春.血浆甲基化septin9基因与结直肠癌相关性的研究进展[J].中华消化杂志,2015,35(5):358-360.
[16] Johnson DA,Barclay RL,Mergener K,et al. Plasma SEPT9 versus fecal immunochemical testing for colorectal cancer screening:a prospective multicenter study[J]. Plos One,2014,9(6):e98238.
[2]刘茉,王亚东,王贵齐,等.基于慢病管理的结直肠癌筛查模式初探[J].中华疾病控制杂志,2015,19(5):524-527.
[3]李世拥,陈纲,杜峻峰,等.腹腔镜右半结肠癌根治术的临床疗效分析[J/CD].中华普外科手术学杂志:电子版,2015,9(1):28-30.
[4]蒋奕玫,赵任.肿瘤标志物在结直肠癌诊断中的作用[J].上海交通大学学报医学版,2015,35(11):1734-1737.
[5] Molnár B,Tóth K,Barták BK,et al. Plasma methylated septin 9:a colorectal cancer screening marker[J]. Expert Rev Mol Diagn,2015,15(2):171-184.
[6] Song L,Li Y. Chapter Four-SEPT9:A Specific Circulating Biomarker for Colorectal Cancer[J]. Adv Clin Chem,2015,72(7):171-204.
[7] Spiliotis ET,Kinoshita M,Nelson WJ. A mitotic septin scaffold required for Mammalian chromosome congression and segregation[J]. Science,2005,307(5716):1781-1785.
[8] Li Y,Song L,Gong Y,et al. Detection of colorectal cancer by DNA methylation biomarker SEPT9:past,present and future[J]. Biomark Med,2014,8(5):755-769.
[9] Payne SR. From discovery to the clinic:the novel DNA methylation biomarker(m)SEPT9 for the detection of colorectal cancer in blood[J]. Epigenomics,2016,2(4):575-585.
[10] Lofton-Day C,Model F,Devos T,et al. DNA methylation biomarkers for blood-based colorectal cancer screening[J]. Clin Chem,2008,54(2):414-423.
[11] 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.
[12] Wasserkort R,Kalmar A,Valcz G,et al. Aberrant septin 9 DNA methylation in colorectal cancer is restricted to a single CpG island[J]. BMC Cancer,2013,13(1):398-398.
[13] Yan S,Liu Z,Yu S,et al. Diagnostic Value of Methylated SEPT9for Colorectal Cancer Screening:A Meta-Analysis[J]. Med Sci Monit,2016,22(9):3409-3418.
[14] Kang Q,Jin P,Yang L,et al. Significance of SEPT9 gene methylation detection of plasma circulation DNA in colorectal cancer screening[J]. Zhonghua Yi Xue Za Zhi,2014,94(48):3839-3841.
[15]贺娜,吴开春.血浆甲基化septin9基因与结直肠癌相关性的研究进展[J].中华消化杂志,2015,35(5):358-360.
[16] Johnson DA,Barclay RL,Mergener K,et al. Plasma SEPT9 versus fecal immunochemical testing for colorectal cancer screening:a prospective multicenter study[J]. Plos One,2014,9(6):e98238.