用三种生物标志物对大肠癌进行检测的意义  

Detection on aberrant CDKN2/p16 gene with serum DNA in colorectal cancer patients

作　　者：张宗[1] 梁小波[2] 刘永锠[3] 

机构地区：[1]山西省肿瘤医院血液内科,太原030013 [2]山西省肿瘤医院肛肠外科,太原030013 [3]山西省肿瘤医院放射生物室,太原030013

出　　处：《肿瘤研究与临床》2006年第4期228-230,共3页Cancer Research and Clinic

基　　金：山西省科研基金资助(022075)

摘　　要：目的寻找一种切实可行的检测肿瘤的生物标志物及其方法。方法对100例结直肠癌患者取血清,另取献血员19例,非肿瘤患者13例为对照;并另取癌组织13份,癌旁组织11份作对比观察,同时用三种方法进行检测。一为对p16基因甲基化分析;二为对其进行缺失分析,三为对其进行点突变的分析。结果患者血清异常甲基化为58%;缺失为14%;点突变为25%;癌组织之结果与血清相似;而癌旁组织显然较低。SSCP阳性者经序列分析证实有3例为错义突变,1例为移位,1例为同义突变。其中4例造成p16蛋白的缺失。作为肿瘤的生物标志物,三项联合应用其灵敏度为75%,特异性为96.87%,准确率为80.30%。比文献用CEA+CA19-9+CA72-4+CA242四项指标联合之灵敏度、特异性、准确率皆高,尤其是特异性。如果仅用甲基化加突变亦与之相当。结论血清DNA含量不高但能反映人体对肿瘤的负荷,实验对DNA的质和量的要求不是太高,能检出10-3的DNA片段,可用于临床诊断及大面积普查,并可用于对出院患者的长期随访。Objective For the purpose of research a biomarker and it＇s relative technique to detect the colorectal cancer. Methods The MSP; SSCP and deletion tests with serum have been taken simultaneously in 1130 cases of colorectal cancer patients and 2 groups of control ,as well as the specimens of 13 cancer and 11 paraneoplastic tissue for a contrast. Results The aberrant methylation rate of p16 in the serum was 58.00 %; Deletion 14.00 %; and suspicious point mutation 25.00 %. The data of cancer tissues is the same as that of the serum .but in paraneoplastic tissue is much lower. 10 cases had been tested by Sequencing analysis. Mutation types： 3 of missense; 1 of frameshift; 1 of nonsense. 4 of them result in p16 protein defect. As a tumour marker, if combined using this 3 tests, it demonstrated the sensitivity of 75.00 %; Specificity of 96.87 % and Accuracy of 80.30 %; it＂ s higher than the results of CEA＋CA19-9＋CA72-4＋CA242 four markers＇ combination. If only examined the MSP and SSCP two tests, the result was equal to the former. Conclusion The content of DNA in serum is not to much, but it reflect the tumour burden of patient. MSP demands the quality or quantity of DNA is not too strict. The 10-3 fragments of DNA could be detected in the serum, it can be used in the clinical diagnosis or popular investigation, and long term postoperative followup.

关 键 词：生物标志物 结直肠癌 

分 类 号：R735.34[医药卫生—肿瘤]