【作者】 吴静；

【导师】 李锐；

【作者基本信息】 苏州大学 ， 内科学（消化系病学）， 2023， 硕士

【摘要】 背景和目的:结直肠癌的发病率、死亡率逐年升高,其发病年龄呈现年轻化趋势,对人类生命健康产生重要危险。早期结直肠癌的筛查和治疗有利于提高结直肠癌患者生存率。粪便DNA甲基化检测技术安全、患者依从性好、灵敏度高、特异度高,在多类临床疾病的诊断和疗效判定中发挥了重要价值。SDC2基因的甲基化发生在结直肠癌早期,其基因编码跨膜硫酸肝素蛋白聚糖,参与血管形成、细胞增殖和细胞迁移,在结肠间充质细胞中表达。当从粪便脱落的肿瘤细胞中检出SDC2基因甲基化,代表有较高的结直肠癌发生风险。本课题旨在研究粪便SDC2甲基化检测在结直肠癌筛查的效果及应用前景。方法:研究对象选择在2021年1月-2022年1月内从苏州永鼎医院以及苏州大学附属第一医院平江院区消化科、江南大学附属医院消化科进行粪便DNA检测的受检者共101 1例,所有患者均接受粪便SDC2甲基化检测。以肠镜结合病理学检查为金标准,评估SDC2甲基化检测在结直肠癌筛查中的诊断效能,探讨SDC2甲基化检测用于结直肠癌筛查的可能性。结果:1011例患者在性别、年龄比较上的差异并无统计学意义(P>0.05),粪便DNA检测结果为阳性有64例,粪便DNA总体阳性率6.33%,之后接受肠镜复查人数为55例,肠镜依从度为85.9%;在DNA检测阴性的947人中,55人自愿进行肠镜筛查,肠镜依从度为5.8%,粪便DNA检测筛查明显影响就诊人群对肠镜的依从性。对粪便DNA阳性的55例后续进行肠镜及病理检测者进行统计,其中结直肠癌3例,腺瘤25例,息肉18例,无异常9例;对粪便DNA阴性病例的肠镜及病理结果进行统计,可以发现息肉48例,无异常7例。在25例肠镜检测为腺瘤的病例中有21人为腺瘤伴瘤变(包括高级别上皮内瘤变、低级别上皮内瘤变),占粪便DNA检测阳性占比人数38.18%;4人为腺瘤无瘤变,占粪便DNA阳性人数的7.27%;所以粪便DNA检测技术对于腺瘤的检出有积极意义。粪便DNA检测与最终病理结果比较,粪便DNA检测灵敏度为86.79%,特异度84.21%,阳性预测值83.64%,阴性预测值87.27%,总符合率为85.45%。结论:粪便SDC2甲基化检测患者顺应性较高,且具有较高的灵敏度和特异度,可能对结直肠癌的早期筛查具有重要价值。更多还原

【Abstract】 Background and Objective:The incidence rate and mortality rate of colorectal cancer are increasing year by year,and the age of onset is younger,which poses an important risk to human life and health.The screening and treatment of early colorectal cancer is beneficial for improving the survival rate of colorectal cancer patients.Fecal DNA methylation detection technology is safe,patient compliance is good,sensitivity is high,and specificity is high.It has played an important role in the diagnosis and efficacy determination of various clinical diseases.The methylation of SDC2 gene occurs in the early stage of colorectal cancer.It encodes transmembrane heparin sulfate proteoglycan,participates in angiogenesis,cell proliferation and cell migration,and is expressed in colon mesenchymal cells.When methylation of the SDC2 gene is detected in tumor cells detached from feces,it represents a higher risk of developing colorectal cancer.This study aims to investigate the effectiveness and application prospects of fecal SDC2 methylation detection in colorectal cancer screening.Methods:From January 2021 to January 2022,a total of 1,011 subjects were selected to undergo fecal DNA testing from the Department of Gastroenterology of Suzhou Yongding Hospital,Pingjiang Branch of the First Affiliated Hospital of Soochow University,and the Department of Gastroenterology of Jiangnan University Affiliated Hospital,and all patients underwent fecal SDC2 methylation testing.Using colonoscopy combined with pathological examination as the gold standard,evaluate the diagnostic efficacy of SDC2 methylation test in colorectal cancer screening,and explore the possibility of using SDC2 methylation test for colorectal cancer screening.Results:Among the 1011 patients,There was no significant difference in sex and age(P>0.05),64 patients had positive fecal DNA test results,and the overall positive rate of fecal DNA was 6.33%,and the number of people who underwent colonoscopy review was 55,and the compliance degree of colonoscopy was 85.9%.Among the 947 people who tested negative for DNA,55 voluntarily underwent colonoscopy screening,and the compliance rate of colonoscopy was 5.8%,and fecal DNA testing screening significantly affected the compliance of the population to colonoscopy.The statistics of 55 cases of fecal DNA positive follow-up colonoscopy and pathological testing were carried out,including 3 cases of colorectal cancer,25 cases of adenomas,18 cases of polyps,and 9 cases of no abnormality.The colonoscopy and pathological results of fecal DNA-negative cases showed that 48 cases of polyps were found and 7 cases were not abnormal.Among the 25 cases of adenoma detected by colonoscopy,21 were adenomas with neoplasia(including high-grade intraepithelial neoplasia and low-grade intraepithelial neoplasia),accounting for 38.18%of the positive fecal DNA test.4 people had adenomas without neoplasia,accounting for 7.27%of the fecal DNA positive population;Therefore,fecal DNA detection technology has positive significance for the detection of adenomas.Compared with the final pathological results,the sensitivity of fecal DNA detection was 86.79%,the specificity was 84.21%,the positive predictive value was 83.64%,the negative predictive value was 87.27%,and the overall compliance rate was 85.45%.Conclusion:Fecal SDC2 methylation test has high compliance,high sensitivity and specificity,which is of great value for early screening of colorectal cancer.更多还原