MALDI-TOF MS在结直肠癌诊断和监测中的应用研究进展

doi:10.3969/j.issn.1673-8640.2026.04.002

摘要/Abstract

摘要：

基因检测目前已广泛应用于结直肠癌的筛查、诊断、分型、监测和治疗方案选择。基质辅助激光解吸电离飞行时间质谱（MALDI-TOF MS）因其高通量、高灵敏度、高检测效率等优势逐渐成为检测核酸多态性的技术之一。文章简述核酸质谱的产生和发展，介绍MALDI-TOF MS检测核酸的原理和方法，同时对MALDI-TOF MS用于结直肠癌的检测靶点、项目、用途和临床价值进行综述。

关键词: 基质辅助激光解吸电离飞行时间质谱, 单核苷酸多态性, 基因修饰, 结直肠癌

Abstract:

Gene testing has been widely applied in the screening，diagnosis，classification，monitoring and treatment of colorectal cancer. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry （MALDI-TOF MS） has gradually become one of the techniques for determining nucleic acid polymorphisms due to its advantages of high throughput，high sensitivity and high determination efficiency. This review briefly describes the origin and development of nucleic acid mass spectrometry，introduces the principle and method of MALDI-TOF MS for nucleic acid determination，and reviews the targets，projects，applications and clinical value of MALDI-TOF MS in colorectal cancer determination.

Key words: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, Single nucleotide polymorphism, Gene modification, Colorectal cancer

中图分类号:

R446.1

范咏冰, 石梦鸽, 曲林琳. MALDI-TOF MS在结直肠癌诊断和监测中的应用研究进展[J]. 检验医学, 2026, 41(4): 318-325.

FAN Yongbing, SHI Mengge, QU Linlin. Research progress on the application of MALDI-TOF MS in the diagnosis and monitoring of colorectal cancer[J]. Laboratory Medicine, 2026, 41(4): 318-325.

图/表 3

参考文献 73

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方法	靶点	样本类型	敏感性	特异性	检测成本
MALDI-TOF MS^[32]	多靶点（甲基化+SNP+ 突变）	血液、粪便、组织	85%~92% （早期）	90%~95%	低（10~50元·样本^-1）
多靶点粪便DNA检测^[33]	KRAS突变+NDRG4/BMP3甲基化+血红蛋白	粪便	92% （晚期）	87%	中（约180美元·样本^-1）
实时荧光定量PCR^[34]	SEPT9甲基化	血液	73%	80%~85%	中（约10.4美元·样本^-1）
多靶点粪便FIT-DNA联合检测技术^[35]	多甲基化标志物	粪便	92%	88%	高（57~224美元·样本^-1）

方法	靶点	样本类型	敏感性	特异性	检测成本
MALDI-TOF MS^[32]	多靶点（甲基化+SNP+ 突变）	血液、粪便、组织	85%~92% （早期）	90%~95%	低（10~50元·样本^-1）
多靶点粪便DNA检测^[33]	KRAS突变+NDRG4/BMP3甲基化+血红蛋白	粪便	92% （晚期）	87%	中（约180美元·样本^-1）
实时荧光定量PCR^[34]	SEPT9甲基化	血液	73%	80%~85%	中（约10.4美元·样本^-1）
多靶点粪便FIT-DNA联合检测技术^[35]	多甲基化标志物	粪便	92%	88%	高（57~224美元·样本^-1）

文献	基因名称	类别	例数	样本类型	风险统计值	用途	临床意义
WU等^[65]	lncRNA MIR155HG	SNP	1 024例	外周血	OR=1.32，95%CI为1.02~1.71，P=0.036	高风险评估	筛查
LIU等^[70]	MMP2	SNP	1 326例	外周血	OR=0.77，95%CI为0.60~0.98，P<0.05	低风险评估	筛查
KIM等^[67]	PAUF	SNP	831例	肿瘤组织	OS：HR^①=1.95，95%CI为1.42~2.67，P<0.000 1 DFS^②：HR=1.59，95%CI为1.21~2.08，P<0.000 1	术后高风险评估	预后监测
KIM等^[67]	TPST1	SNP	831例	肿瘤组织	DFS：HR=2.65，95%CI为1.58~4.45，P=0.000 2	术后高风险评估	预后监测
LI等^[71]	ADCY9	SNP	1 022例	外周血	OR=3.54，95%CI为1.16~10.86，P=0.027	高风险评估	筛查
CHEN等^[56]	PTGER4	DNA甲基化	208例	肿瘤组织	OS：HR=4.32，95%CI为1.80~10.50，P=0.007	术后高风险评估	预后监测
CHEN等^[56]	ZNF43	DNA甲基化	208例	肿瘤组织	RFS：HR=2.33，95%CI为1.07~5.08，P<0.001	术后高风险评估	预后监测
文献	基因名称	类别	例数	样本类型	风险统计值	用途	临床意义
LIN等^[38]	lncRNA DLX6-AS1	DNA甲基化	433例	肿瘤组织	OS：HR=1.64，95%CI为1.02~2.64，P=0.042	预测标志物	诊断、监测
WU等^[48]	SMAD7	SNP	1 392例	外周血	OR=1.31，95%CI为1.04~1.67，P=0.024	预测标志物	诊断、监测
CEVIK等^[72]	PD-1/PDL-1	SNP	189例	外周血	OR=0.068，95%CI为0.02~0.21，P<0.001	预后标志物	预后监测
CHANG等^[64]	PRR相关基因	SNP	117例	肿瘤组织	OS：HR=4.674，95%CI为1.42~16.04，P=0.011	预后标志物	预后监测
CHEN等^[73]	ALOX5	SNP	300例	外周血	OS：HR=3.32，95%CI为1.51~7.27，P=0.003	预测标志物	预后监测
DOMINGUEZ-VALENTIN等^[36]	致病性MMR相关基因	SNP	569例	外周血	HR=1.49，95%CI为1.06~2.09，P=0.030	预测标志物	预测、诊断

文献	基因名称	类别	例数	样本类型	风险统计值	用途	临床意义
WU等^[65]	lncRNA MIR155HG	SNP	1 024例	外周血	OR=1.32，95%CI为1.02~1.71，P=0.036	高风险评估	筛查
LIU等^[70]	MMP2	SNP	1 326例	外周血	OR=0.77，95%CI为0.60~0.98，P<0.05	低风险评估	筛查
KIM等^[67]	PAUF	SNP	831例	肿瘤组织	OS：HR^①=1.95，95%CI为1.42~2.67，P<0.000 1 DFS^②：HR=1.59，95%CI为1.21~2.08，P<0.000 1	术后高风险评估	预后监测
KIM等^[67]	TPST1	SNP	831例	肿瘤组织	DFS：HR=2.65，95%CI为1.58~4.45，P=0.000 2	术后高风险评估	预后监测
LI等^[71]	ADCY9	SNP	1 022例	外周血	OR=3.54，95%CI为1.16~10.86，P=0.027	高风险评估	筛查
CHEN等^[56]	PTGER4	DNA甲基化	208例	肿瘤组织	OS：HR=4.32，95%CI为1.80~10.50，P=0.007	术后高风险评估	预后监测
CHEN等^[56]	ZNF43	DNA甲基化	208例	肿瘤组织	RFS：HR=2.33，95%CI为1.07~5.08，P<0.001	术后高风险评估	预后监测
文献	基因名称	类别	例数	样本类型	风险统计值	用途	临床意义
LIN等^[38]	lncRNA DLX6-AS1	DNA甲基化	433例	肿瘤组织	OS：HR=1.64，95%CI为1.02~2.64，P=0.042	预测标志物	诊断、监测
WU等^[48]	SMAD7	SNP	1 392例	外周血	OR=1.31，95%CI为1.04~1.67，P=0.024	预测标志物	诊断、监测
CEVIK等^[72]	PD-1/PDL-1	SNP	189例	外周血	OR=0.068，95%CI为0.02~0.21，P<0.001	预后标志物	预后监测
CHANG等^[64]	PRR相关基因	SNP	117例	肿瘤组织	OS：HR=4.674，95%CI为1.42~16.04，P=0.011	预后标志物	预后监测
CHEN等^[73]	ALOX5	SNP	300例	外周血	OS：HR=3.32，95%CI为1.51~7.27，P=0.003	预测标志物	预后监测
DOMINGUEZ-VALENTIN等^[36]	致病性MMR相关基因	SNP	569例	外周血	HR=1.49，95%CI为1.06~2.09，P=0.030	预测标志物	预测、诊断