本文選題：大腸癌 + 甲基化　； 參考：《河北北方學(xué)院》2017年碩士論文

【摘要】：SEPT9基因甲基化檢測是美國食品藥品管理局(Food and Drug Administration,FDA)、歐盟(conformite europeenne,CE)認(rèn)證和中國食品藥品監(jiān)督管理總局(China Food and Drug Administration,CFDA)批準(zhǔn)的用于大腸癌篩查(FDA)和/或早期檢測(CE、CFDA)的基因甲基化外周血檢測,是世界上第一個獲得FDA批準(zhǔn)的表觀遺傳學(xué)腫瘤液態(tài)活檢檢測。雖然此檢測在大腸癌篩查和早期檢測的性能已經(jīng)得到廣泛的驗證,但各種影響因素對其性能的影響還未有系統(tǒng)性的研究,其對大腸癌前疾病的檢測性能也缺乏足夠的數(shù)據(jù)。本研究旨在探討患者性別、年齡、癌癥分期、癌癥部位和算法等因素對此檢測性能的影響,并明確此檢測對大腸癌前疾病,包括各型腺瘤及息肉的檢測性能。本研究以機(jī)會性篩查方法共入組428名受試者,其中包括98名大腸癌患者,86名各型腺瘤患者,67名增生性息肉患者和177名無疾病受試者。本研究運用實時熒光定量多聚酶鏈?zhǔn)椒磻?yīng)(qRT-PCR)對SEPT9基因啟動子區(qū)域的甲基化水平進(jìn)行檢測,試驗采用ABI7500 Fast DX熒光定量PCR儀和Epi proColon 2.0 CE試劑盒進(jìn)行檢測。所有血液樣品采集、運輸、處理、血漿提取、DNA保存、亞硫酸鹽轉(zhuǎn)化、PCR、數(shù)據(jù)分析和判讀等操作均遵循Epi proColon 2.0 CE試劑盒說明書進(jìn)行。統(tǒng)計學(xué)分析和制圖采用GraphPad PRISM 5.0軟件完成。研究結(jié)果表明:1/3算法在大腸癌、腺瘤、增生性息肉的陽性檢出率(positive detection rate,PDR)均高于2/3算法,然而,其在正常人中的假陽性率也高于2/3算法。不論采取何種算法,SEPT9檢測對0期和I期大腸癌的陽性檢出率顯著低于對II~IV期大腸癌的陽性檢出率。然而,SEPT9檢測對0期和I期大腸癌的檢出率均超過50%,說明其可以應(yīng)用于大腸早癌篩查。60歲以上正常人群的陽性率顯著高于小于60歲的人群,而在小于60歲人群中,SEPT9檢測的陽性率隨年齡組增高而逐漸遞增。與此相對,大腸癌人群的陽性檢出率在各年齡組間無顯著性差異。進(jìn)一步研究顯示,大腸癌患者的陽性檢出率在各大腸癌分期均未顯示性別方面的差異,在結(jié)直腸各個部位,包括回盲部、升結(jié)腸、橫結(jié)腸、降結(jié)腸、乙狀結(jié)腸、直腸,SEPT9檢測的陽性檢出率也沒有發(fā)現(xiàn)顯著性差異。針對腺瘤的分型檢測顯示,若使用1/3算法,鋸齒狀腺瘤(serrated adenoma,SA)的PDR為27.8%,管狀腺瘤(tubular adenoma,TA)的PDR為28.7%,管狀絨毛腺瘤(tubulovillous adenoma,TVA)的PDR為53.7%,絨毛狀腺瘤(villous adenoma,VA)的PDR為83.3%,表明PDR與腺瘤中絨毛成分的含量呈正相關(guān)。對TVA和VA的高陽性檢出率說明SEPT9檢測可用于癌前進(jìn)展期腺瘤(advanced adenoma,AA)的篩查。我們的研究說明,算法、癌癥分期和受檢者年齡對SEPT9檢測的性能有影響,而性別和癌癥部位對檢測性能沒有影響。SEPT9檢測對含絨毛成分的腺瘤有較高的靈敏度,而對增生性息肉的檢出率較低,因此,它可作為進(jìn)展期腺瘤及早期大腸癌的血液篩查工具。
[Abstract]:The SEPT9 gene methylation test was approved by the Food and Drug Administration (FDA), the Food and Drug Administration (and Drug), the European Union (EU), and the China Food and Drug Administration (CFDA-approved) for the screening of colorectal cancer and / or early detection for peripheral blood methylation. It is the first liquid biopsy of epigenetic tumors approved by FDA in the world. Although the performance of this test has been widely verified in colorectal cancer screening and early detection, the influence of various factors on its performance has not been systematically studied, and the detection performance of colorectal cancer precancerous disease is also lack of sufficient data. The purpose of this study was to investigate the effect of sex, age, stage, location and algorithm of cancer on the detection of precancerous diseases, including adenomas and polyps. In this study, a total of 428 subjects were enrolled by opportunistic screening, including 98 patients with colorectal cancer and 86 patients with adenoma of various types, 67 patients with proliferative polyps and 177 subjects without disease. In this study, the methylation level of promoter region of SEPT9 gene was detected by real-time fluorescence quantitative polymerase chain reaction (QRT-PCR), and ABI7500 Fast DX fluorescence quantitative PCR assay and Epi proColon 2.0 CE kit were used to detect the methylation level. All blood samples were collected, transported, processed, plasma extracted and preserved, sulfite transformed into PCRs, data analysis and interpretation were performed according to the instructions of Epi proColon 2.0 CE kit. Statistical analysis and cartography were completed by GraphPad PRISM 5.0 software. The results show that the positive detection positive rate of positive polyps in colorectal cancer, adenoma and proliferative polyps is higher than that in the control group. However, the false positive rate is also higher in the normal population than that in the control group. The positive rate of SEPT9 in stage 0 and stage I colorectal cancer was significantly lower than that in II~IV stage of colorectal cancer. However, the detection rate of stage 0 and stage I colorectal cancer by SEPT9 was more than 50, which indicated that the positive rate of SEPT9 was significantly higher than that of those aged less than 60 years in the normal population over 60 years of age. The positive rate of SEPT9 increased with the increase of age group. In contrast, there was no significant difference in the positive rate of colorectal cancer among different age groups. Further studies showed that there was no gender difference in the positive rate of colorectal cancer in all stages of colorectal cancer, including ileocecal, ascending, transverse, descending, sigmoid colon, There was no significant difference in the positive rate of SEPT9 in rectal cancer. For adenoma typing, if you use the 1 / 3 algorithm, The PDR of serrated adenoma was 27.8, the PDR of tubular adenoma was 28.7, the PDR of tubulovillous adenoma was 53.7 and the PDR of villous adenoma was 83.3, which indicated that PDR was positively correlated with the content of chorionic component in tubulovillous adenoma. The high positive rates of TVA and VA suggest that SEPT9 can be used to screen advanced adenoma. Our study shows that the algorithm, cancer stage and age of the person tested have influence on the performance of SEPT9 detection, but gender and cancer location have no effect on the detection performance. SEPT9 detection has high sensitivity to adenoma containing villi. But the detection rate of proliferative polyps is low, so it can be used as a blood screening tool for advanced adenoma and early colorectal cancer.
【學(xué)位授予單位】：河北北方學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R735.34

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相關(guān)期刊論文 前1條

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