联合检测SDC2和SFRP2甲基化在结直肠癌筛查中的价值

摘要

Objective To explore the value of methylation of SDC2 and SFRP2 genes promoter in fecal DNA for colorectal cancer ( CRC) screening. Methods All stool samples were enrolled from Changhai Hospital of Naval Medical University, the Tenth People' s Hospital of Tongji University and the Seventh Medical Center of Chinese People's Liberation Army General Hospital. A total of 500 stool samples collected from March 2018 to December 2018 were allocated to CRC group ( 132 CRCs ) , adenoma group ( 38 advanced adenomas), healthy group (152 healthy individuals), interferential group (178 cases of benign colorectal disease or other non-colorectal tumors) and negative group (330 cases composed of healthy group and interferential group ) . The promoter methylation of fecal SDC2 and SFRP2 genes was detected by methylation-specific PCR (MSP) and compared with single gene methylation and the fecal immunochemical tests ( FIT) to evaluate its sensitivity and specificity. Results The stool sample analysis showed that the sensitivity of combined detection of SDC2 and SFRP2 in CRC group was 97. 73％ ( 129/132 ) , which was significantly higher than those of the single gene SDC2 test [ 70. 45％ ( 93/132) , P=0. 000] , single SFRP2 test [81. 82％ (108/132), P=0. 000] and FIT [69. 70％ (92/132), P=0. 000]. In adenoma group, the sensitivity of combined detection of SDC2 and SFRP2 was 57. 89％ (22/38), which was significantly higher than those of the single gene SDC2 test [ 15. 79％ ( 6/38 ) , P= 0. 000 ] and FIT [ 21. 05％ ( 8/38 ) , P=0. 021] , with no significant difference compared with that of SFRP2 test [ 47. 37％ ( 18/38) , P=0. 358] . In healthy group, the specificity of combined detection of SDC2 and SFRP2 was 98. 68％ (150/152), with no significant difference compared with those of single gene SDC2 test [ 100. 00％( 152/152) , P=0. 156] , single SFRP2 test [98. 68％ (150/152), P=1. 000] or FIT [95. 39％ (145/152), P=0. 091]. Specificities of combined detection of two genes in interferential and negative groups were 90. 45％ ( 161/178) and 94. 24％( 311/330) , which were significantly higher than 73. 03％( 130/178, P=0. 000) and 83. 33％( 275/330, P=0. 000) of FIT, respectively. Conclusion The combined detection test of methylation of SDC2 and SFRP2 is superior to single gene test, whose sensitivity of CRC and aggressive adenoma and specificity of distinguishing benign and malignant lesions are higher than FIT, which has potential application value.%目的 评价在粪便样本中联合检测SDC2和SFRP2基因启动子甲基化在结直肠癌筛查中的应用价值.方法 选取海军军医大学长海医院、同济大学附属第十人民医院以及解放军总医院第七医学中心2018年3月至2018年12月收治的500例患者粪便标本,其中结直肠癌132例为肠癌组,进展期腺瘤38例为腺瘤组,健康标本152例为健康组,存在其他肠道病变或非肠癌肿瘤的178例为干扰组,健康组与干扰组共同构成330例肠癌与进展期腺瘤阴性的阴性组.应用甲基化特异度PCR(methylation-specific PCR,MSP)法对上述患者粪便中SDC2和SFRP2基因启动子甲基化进行检测,并与单个基因甲基化检测和粪便免疫潜血试验(FIT)的检测性能相比较,评价其筛查结直肠癌的灵敏度和特异度.结果 SDC2和SFRP2两基因联合检测在肠癌组中的灵敏度为97.73％(129/132),显著高于单基因SDC2检测[70.45％(93/132),P=0.000]、SFRP2检测[81.82％(108/132),P=0.000]以及FIT检测[69.70％(92/132),P=0.000].腺瘤组中SDC2和SFRP2联合检测的灵敏度为57.89％(22/38),显著高于单基因SDC2检测[15.79％(6/38),P=0.000]、FIT检测[21.05％(8/38),P=0.021],与单基因SFRP2检测差异无统计学意义[47.37％(18/38),P=0.358].在健康组中,SDC2和SFRP2联合检测的特异度为98.68％(150/152),与单基因SDC2[100.00％(152/152),P=0.156]、SFRP2[98.68％(150/152),P=1.000]以及FIT[95.39％(145/152),P=0.091]相比,差异无统计学意义.在干扰组以及阴性组中,两基因联合检测的特异度分别为90.45％(161/178)和94.24％(311/330),均显著高于FIT[73.03％(130/178),P=0.000;83.33％(275/330),P=0.000].结论 粪便中SDC2和SFRP2两基因联合检测优于单基因检测,在肠癌、进展期腺瘤的灵敏度以及在区分良性息肉、其他癌种或非癌肠道病变的特异度上均显著高于FIT,具有潜在的应用价值.