结直肠癌患者血浆甲基化Sept9基因的表达及临床意义
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摘要
目的:探讨甲基化Sept9基因在结直肠癌患者血浆中的表达及临床意义。方法:选择2015年1月~2017年3月经陕西省人民医院病理证实的结直肠癌患者87例(结直肠癌组)、结直肠息肉患者79例(结直肠息肉组)、健康体检者93例(健康对照组)作为研究对象,采用实时荧光定量聚合酶链式反应(PCR)技术检测其外周血血浆Sept9基因甲基化情况,比较三组甲基化Sept9基因阳性表达率,分析甲基化Sept9基因阳性表达与结直肠癌病理特征的关系。结果:血浆甲基化Sept9基因在结直肠癌组、结直肠息肉组、健康对照组的阳性表达率分别为71.26%(62/87)、5.06%(4/79)、3.23%(3/93),差异有统计学意义(P<0.05);血浆甲基化Sept9基因阳性表达与结直肠癌患者的性别、年龄、肿瘤部位、病理分型、血管侵犯、神经侵犯无关(P>0.05),与肿瘤最大径、浸润深度、分化程度、淋巴结转移、TNM分期有关(P<0.05);结直肠癌患者血浆甲基化Sept9基因阳性表达率为71.26%(62/87),高于血清CEA的54.02%(47/87)、CA199的35.63%(31/87)、CA724的33.33%(29/87)、CA125的21.84%(19/87),差异有统计学意义(P<0.05)。结论:结直肠癌患者外周血血浆甲基化Sept9基因呈高表达状态,早期检测甲基化Sept9基因表达水平在结直肠癌的诊断及病情评估中有重要意义。
Objective: To explore the expression and clinical significance of plasma methylated Sept9 gene in patients with colorectal cancer. Methods: A total of 87 patients with colorectal cancer(colorectal cancer group), 79 patients with colorectal polyps(colorectal polyps group), who were confirmed by pathology in shanxi province people's hospital from January 2015 to March 2017, and 93 healthy volunteers(healthy control group) were chosen as subjects. The Quantitative Real-time Polymerase Chain Reaction(PCR) technique was used to detected the methylated of Sept9 gene in peripheral blood plasma. The positive expression rates of methylated Sept9 gene in the three groups were compared. The relationship between positive expression of methylated Sept9 gene and pathological features of colorectal carcinoma was analyzed. Results: The positive expression rates of plasma methylated Sept9 gene in the colorectal cancer group, the colorectal polyps group and the healthy control group were 71.26%(62/87), 5.06%(4/79) and 3.23%(3/93) respectively,the differences were statistically significant(P<0.05). The positive expression of plasma methylated Sept9 gene was not related to the gender, age, tumor location, pathological type, vascular invasion and nerve invasion in the patients with colorectal cancer(P>0.05), but related to the maximum tumor diameter, infiltrating depth, differentiation degree, lymphatic metastasi and TNM staging(P<0.05). The positive expression rate [71.26%(62/87))] of plasma methylated Sept9 gene in the patients with colorectal cancer were higher than that54.02%(47/87) of serum CEA, 35.63%(31/87) of CA199, 33.33%(29/87) of CA724 and 21.84%(19/87) of CA125, the differences were statistically significant(P<0.05). Conclusion: The plasma methylated Sept9 gene is highly expressed in the patients with colorectal cancer, so early detection of the expression level of the methylated Sept9 gene has important significance in the early diagnosis and assessment of colorectal cancer.
Objective: To explore the expression and clinical significance of plasma methylated Sept9 gene in patients with colorectal cancer. Methods: A total of 87 patients with colorectal cancer(colorectal cancer group), 79 patients with colorectal polyps(colorectal polyps group), who were confirmed by pathology in shanxi province people's hospital from January 2015 to March 2017, and 93 healthy volunteers(healthy control group) were chosen as subjects. The Quantitative Real-time Polymerase Chain Reaction(PCR) technique was used to detected the methylated of Sept9 gene in peripheral blood plasma. The positive expression rates of methylated Sept9 gene in the three groups were compared. The relationship between positive expression of methylated Sept9 gene and pathological features of colorectal carcinoma was analyzed. Results: The positive expression rates of plasma methylated Sept9 gene in the colorectal cancer group, the colorectal polyps group and the healthy control group were 71.26%(62/87), 5.06%(4/79) and 3.23%(3/93) respectively,the differences were statistically significant(P<0.05). The positive expression of plasma methylated Sept9 gene was not related to the gender, age, tumor location, pathological type, vascular invasion and nerve invasion in the patients with colorectal cancer(P>0.05), but related to the maximum tumor diameter, infiltrating depth, differentiation degree, lymphatic metastasi and TNM staging(P<0.05). The positive expression rate [71.26%(62/87))] of plasma methylated Sept9 gene in the patients with colorectal cancer were higher than that54.02%(47/87) of serum CEA, 35.63%(31/87) of CA199, 33.33%(29/87) of CA724 and 21.84%(19/87) of CA125, the differences were statistically significant(P<0.05). Conclusion: The plasma methylated Sept9 gene is highly expressed in the patients with colorectal cancer, so early detection of the expression level of the methylated Sept9 gene has important significance in the early diagnosis and assessment of colorectal cancer.
引文
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[27]Li Y,Song L,Gong Y,et al.Detection of colorectal cancer by DNA methylation biomarker SEPT9:past,present and future[J].Biomark Med,2014,8(5):755-769
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[29]何琼,王冕,周建文,等.多重Methy Light在结直肠癌相关基因ALX4和SEPT9甲基化检测中的应用[J].中山大学学报(医学科学版),2015,36(5):657-662He Qiong,Wang Mian,Zhou Jian-wen,et al.Detection of ALX4 and SEPT9 Methylation in Human Colorectal Cancer by Multiplex Methy Light Assay[J].Journal of Sun Yat-sen University(Medical Sciences),2015,36(5):657-662
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[2]Gargalionis AN,Papavassiliou AG.Liquid Biopsies in Colorectal Cancer:Monitoring Genetic Heterogeneity[J].Trends Cancer,2017,3(3):166-168
[3]夏秀娟,李粉婷,刘佳,等.转移性结直肠癌抗血管生成靶向治疗的研究进展[J].现代生物医学进展,2016,16(1):187-191Xia Xiu-juan,Li Fen-ting,Liu Jia,et al.Anti-angiogenesis Targeted Therapy for Metastatic Colorectal Cancer:Current Situation and Future Perspectives[J].Progress in Modern Biomedicine,2016,16(1):187-191
[4]Adam R,de Gramont A,Figueras J,et al.Managing synchronous liver metastases from colorectal cancer:a multidisciplinary international consensus[J].Cancer Treat Rev,2015,41(9):729-741
[5]Kahi CJ,Boland CR,Dominitz JA,et al.Colonoscopy Surveillance After Colorectal Cancer Resection:Recommendations of the US MultiSociety Task Force on Colorectal Cancer[J].Gastroenterology,2016,150(3):758-768.e11
[6]Co?kun?,?ztopuz?,?zkan?F.Determination of IL-6,TNF-αand VEGF levels in the serums of patients with colorectal cancer[J].Cell Mol Biol(Noisy-le-grand),2017,63(5):97-101
[7]Tolstrup J,Madsen RC,Sneftrup MV,et al.Greenlandic patients with colorectal cancer:symptomatology,primary investigations and differences in diagnostic intervals between Nuuk and the rest of the country[J].Int J Circumpolar Health,2017,76(1):1344086
[8]Behrouz Sharif S,Hashemzadeh S,Mousavi Ardehaie R,et al.Detection of aberrant methylated SEPT9 and NTRK3 genes in sporadic colorectal cancer patients as a potential diagnostic biomarker[J].Oncol Lett,2016,12(6):5335-5343
[9]Song L,Peng X,Li Y,et al.The SEPT9 gene methylation assay is capable of detecting colorectal adenoma in opportunistic screening[J].Epigenomics,2017,9(5):599-610
[10]Song L,Li Y.Progress on the clinical application of the SEPT9 gene methylation assay in the past 5 years[J].Biomark Med,2017,11(6):415-418
[11]Wu D,Zhou G,Jin P,et al.Detection of Colorectal Cancer Using a Simplified SEPT9 Gene Methylation Assay Is a Reliable Method for Opportunistic Screening[J].J Mol Diagn,2016,18(4):535-545
[12]Potter NT,Hurban P,White MN,et al.Validation of a real-time PCR-based qualitative assay for the detection of methylated SEPT9DNA in human plasma[J].Clin Chem,2014,60(9):1183-1191
[13]Tham C,Chew M,Soong R,et al.Postoperative serum methylation levels of TAC1 and SEPT9 are independent predictors of recurrence and survival of patients with colorectal cancer[J].Cancer,2014,120(20):3131-3141
[14]Gonzalez M,Gervaz P.Risk factors for survival after lung metastasectomy in colorectal cancer patients:systematic review and meta-analysis[J].Future Oncol,2015,11(2 Suppl):31-33
[15]Lee JY,Ock M,Jo MW,et al.Estimating utility weights and qualityadjusted life year loss for colorectal cancer-related health states in Korea[J].Sci Rep,2017,7(1):5571
[16]Swain SK,Zirpe D,Das S,et al.Parietal Wall Abscess Perforating to Transverse Colon:A Rare Presentation[J].J Clin Diagn Res,2017,11(5):PD10-PD11
[17]Latchana N,Esemuede I,Harzman A,et al.Colonoscope-medi ated vaginoscopy for diagnostic evaluation of colovaginal fistulas[J].Tech Coloproctol,2017,21(5):397-399
[18]Jiang K,Sun Y,Wang C,et al.Genome-wide association study identifies two new susceptibility loci for colorectal cancer at 5q23.3 and17q12 in Han Chinese[J].Oncotarget,2015,6(37):40327-40336
[19]Dolan NC,Ramirez-Zohfeld V,Rademaker AW,et al.The Effectiveness of a Physician-Only and Physician-Patient Intervention on Colorectal Cancer Screening Discussions Between Providers and African American and Latino Patients[J].J Gen Intern Med,2015,30(12):1780-1787
[20]Lopes-Ramos CM,Barros BP,Koyama FC,et al.E2F1 somatic mutation within mi RNA target site impairs gene regulation in colorectal cancer[J].PLo S One,2017,12(7):e0181153
[21]Sorich MJ,Wiese MD,Rowland A,et al.Extended RAS mutations and anti-EGFR monoclonal antibody survival benefit in metastatic colorectal cancer:a meta-analysis of randomized,controlled trials[J].Ann Oncol,2015,26(1):13-21
[22]Ni HB,Wang FY,Xu J,et al.Screening and identification of a tumor specific methylation phenotype in the colorectal laterally spreading tumor[J].Eur Rev Med Pharmacol Sci,2017,21(11):2611-2616
[23]Duan BS,Xie LF,Wang Y.Aberrant Methylation of T-cadherin Can Be a Diagnostic Biomarker for Colorectal Cancer[J].Cancer Genomics Proteomics,2017,14(4):277-284
[24]Nian J,Sun X,Ming S,et al.Diagnostic Accuracy of Methylated SEPT9 for Blood-based Colorectal Cancer Detection:A Systematic Review and Meta-Analysis[J].Clin Transl Gastroenterol,2017,8(1):e216
[25]Song L,Yu H,Jia J,et al.A systematic review of the performance of the SEPT9 gene methylation assay in colorectal cancerscreening,monitoring,diagnosis and prognosis[J].Cancer Biomark,2017,18(4):425-432
[26]Jin P,Kang Q,Wang X,et al.Performance of a second-generation methylated SEPT9 test in detecting colorectal neoplasm[J].J Gastroenterol Hepatol,2015,30(5):830-833
[27]Li Y,Song L,Gong Y,et al.Detection of colorectal cancer by DNA methylation biomarker SEPT9:past,present and future[J].Biomark Med,2014,8(5):755-769
[28]Ravegnini G,Zolezzi Moraga JM,Maffei F,et al.Simultaneous Analysis of SEPT9 Promoter Methylation Status,Micronuclei Frequency,and Folate-Related Gene Polymorphisms:The Potential for a Novel Blood-Based Colorectal Cancer Biomarker[J].Int J Mol Sci,2015,16(12):28486-28497
[29]何琼,王冕,周建文,等.多重Methy Light在结直肠癌相关基因ALX4和SEPT9甲基化检测中的应用[J].中山大学学报(医学科学版),2015,36(5):657-662He Qiong,Wang Mian,Zhou Jian-wen,et al.Detection of ALX4 and SEPT9 Methylation in Human Colorectal Cancer by Multiplex Methy Light Assay[J].Journal of Sun Yat-sen University(Medical Sciences),2015,36(5):657-662
[30]Havermann S,Chovolou Y,Humpf HU,et al.Modulation of the Nrf2signalling pathway in Hct116 colon carcinoma cells by baicalein and itsmethylated derivative negletein[J].Pharm Biol,2016,54(9):1491-1502