Septin9基因甲基化和SDC2基因甲基化联合检测辅助诊断结直肠癌

doi:10.3969/j.issn.1673-8640.2025.06.001

摘要/Abstract

摘要：

目的探讨血浆Septin9基因甲基化和粪便SDC2基因甲基化联合检测在结直肠癌（CRC）诊断中的临床应用价值。方法选取2023年11月—2024年1月复旦大学附属肿瘤医院CRC患者110例[CRC组，包括早期（TNM分期Ⅰ~Ⅱ期）患者48例（早期CRC组）、晚期（TNM分期Ⅲ~Ⅳ期）患者62例（晚期CRC组）]、结直肠良性肿瘤患者21例（疾病对照组）、健康体检者37名（正常对照组）。检测所有研究对象血清癌胚抗原（CEA）、糖类抗原19-9（CA19-9）水平和粪便SDC2基因甲基化、血浆Septin9基因甲基化水平。采用一致性检验分析血浆Septin9基因甲基化与粪便SDC2基因甲基化检测结果的一致性。采用受试者工作特征（ROC）曲线评价各项指标联合检测诊断CRC的效能。结果与正常对照组比较，疾病对照组和CRC组SDC2基因甲基化阳性率均显著升高（P<0.01）；CRC组Septin9基因甲基化阳性率显著升高（P<0.001），且早期CRC组、晚期CRC组SDC2基因甲基化和Septin9基因甲基化阳性率均显著升高（P<0.001）。疾病对照组与正常对照组之间Septin9基因甲基化阳性率差异无统计学意义（P>0.05）。除正常对照组（Kappa=0.358，P=0.026）外，其他各组SDC2基因甲基化与Septin9基因甲基化均无一致性（P>0.05）。SDC2基因+Septin9基因+CA19-9联合检测模型诊断CRC的曲线下面积（AUC）为0.958，最佳临界值为0.571，敏感性为95.5%，特异性为90.3%；诊断早期CRC的AUC为0.940，最佳临界值为0.700，敏感性为91.7%，特异性为90.3%。结论 Septin9基因甲基化、SDC2基因甲基化与传统肿瘤标志物CA19-9联合检测有助于提高CRC的诊断效能。

关键词: Septin9基因, SDC2基因, 甲基化, 结直肠癌

Abstract:

Objective To investigate the clinical application value of combined determination of plasma Septin9 gene methylation and fecal SDC2 gene methylation in the diagnosis of colorectal cancer（CRC）. Methods A total of 110 CRC patients from Fudan University Shanghai Cancer Center from November 2023 to January 2024 were enrolled as CRC group，which included 48 patients in the early stage（TNM stage Ⅰ-Ⅱ）（early CRC group），62 patients in the advanced stage（TNM stage Ⅲ-Ⅳ）（advanced CRC group）. Totally，21 patients with benign colorectal tumors（disease control group） and 37 healthy subjects（healthy control group） were enrolled as well. The levels of serum carcinoembryonic antigen（CEA） and carbohydrate antigen（CA19-9），as well as the methylation levels of fecal SDC2 gene and plasma Septin9 gene were determined. The consistency of plasma Septin9 gene methylation and fecal SDC2 gene methylation determination results was evaluated. The efficacy of combined determination of various indicators in the diagnosis of CRC was evaluated by receiver operating characteristic（ROC） curve. Results Compared with healthy control group，the positive rates of SDC2 gene methylation in both disease control group and CRC group were increased（P<0.01）. The positive rate of Septin9 gene methylation in CRC group was increased（P<0.001）. The positive rates of SDC2 gene methylation and Septin9 gene methylation in both early CRC group and advanced CRC group were increased（P<0.001）. There was no statistical significance in the positive rate of Septin9 gene methylation between disease control group and healthy control group（P>0.05）. Except for healthy control group（Kappa=0.358，P=0.026），there was no consistency in the methylation of SDC2 gene and Septin9 gene in the other groups（P>0.05）. The area under curve（AUC） of the combined determination of SDC2 gene+Septin9 gene+CA19-9 in diagnosing CRC was 0.958，the optimal cut-off value was 0.571，the sensitivity was 95.5%，and the specificity was 90.3%. The AUC for diagnosing early CRC was 0.940，the optimal cut-off value was 0.700，the sensitivity was 91.7%，and the specificity was 90.3%. Conclusions The combined determination of Septin9 gene methylation，SDC2 gene methylation and the traditional tumor marker CA19-9 is helpful to improve the diagnostic efficacy of CRC.

Key words: Septin9 gene, SDC2 gene, Methylation, Colorectal cancer

中图分类号:

R446.7

黄仁, 施卫忠, 卢仁泉, 郭林, 王砚春. Septin9基因甲基化和SDC2基因甲基化联合检测辅助诊断结直肠癌[J]. 检验医学, 2025, 40(6): 519-524.

HUANG Ren, SHI Weizhong, LU Renquan, GUO Lin, WANG Yanchun. Combined determination of Septin9 gene methylation and SDC2 gene methylation in auxiliary diagnosis of colorectal cancer[J]. Laboratory Medicine, 2025, 40(6): 519-524.

图/表 5

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组别	例数	CEA/（ng·mL^-1）	CA19-9/（U·mL^-1）
正常对照组	37	1.72（0.67，2.24）	5.74（2.69，6.50）
疾病对照组	21	2.48（1.13，2.28）	9.37（3.37，14.65）
CRC组	110	3.31（1.72，9.10）^**#	11.10（6.28，21.70）^*
早期CRC组	48	2.36（1.35，4.42）	9.51（5.37，16.45）^*
晚期CRC组	62	4.96（2.36，22.7）^**##	12.35（7.35，31.28）^*

组别	例数	CEA/（ng·mL^-1）	CA19-9/（U·mL^-1）
正常对照组	37	1.72（0.67，2.24）	5.74（2.69，6.50）
疾病对照组	21	2.48（1.13，2.28）	9.37（3.37，14.65）
CRC组	110	3.31（1.72，9.10）^**#	11.10（6.28，21.70）^*
早期CRC组	48	2.36（1.35，4.42）	9.51（5.37，16.45）^*
晚期CRC组	62	4.96（2.36，22.7）^**##	12.35（7.35，31.28）^*

组别	例数	SDC2基因甲基化/[%（例）]	Septin9基因甲基化/[%（例）]
正常对照组	37	8.1（3）	5.4（2）
疾病对照组	21	42.9（9）^*	9.5（2）
CRC组	110	88.2（97）^**	42.7（47）^**
早期CRC组	48	89.6（43）^**	31.3（15）^*
晚期CRC组	62	87.1（54）^**	51.6（32）^**

组别	例数	SDC2基因甲基化/[%（例）]	Septin9基因甲基化/[%（例）]
正常对照组	37	8.1（3）	5.4（2）
疾病对照组	21	42.9（9）^*	9.5（2）
CRC组	110	88.2（97）^**	42.7（47）^**
早期CRC组	48	89.6（43）^**	31.3（15）^*
晚期CRC组	62	87.1（54）^**	51.6（32）^**