本文選題：結(jié)直腸癌 + KRAS基因　； 參考：《河北醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:本課題主要通過檢測MMR蛋白在散發(fā)性CRC中的表達情況,分析MSI-H CRC與MSI-L/MSS CRC的臨床病理特征。在明確MSI分型的前提下,檢測KRAS基因在CRC的突變率,分析其與MSI分型之間的關(guān)聯(lián)性。以KRAS基因突變、MSI分型將CRC患者分為A組KRAS基因野生型MSS/MSI-L、B組KRAS基因野生型MSI-H、C組KRAS基因突變型MSS/MSI-L、D組KRAS基因突變型MSI-H四組,分析不同組間臨床病理特征的差異。方法:隨機選取2015年2月至2016年12月就診于我院行CRC手術(shù)切除治療的患者743例,排除遺傳性腺瘤性息肉病和林奇綜合征患者,于我院病案室借閱患者的相關(guān)病例資料,收集患者的基本信息及臨床數(shù)據(jù)、患者術(shù)后KRAS基因檢測結(jié)果,應(yīng)用免疫組化法檢測患者MMR蛋白(MLH1、MSH2、MSH6和PMS2)表達并收集資料,結(jié)果數(shù)據(jù)使用SPSS 20統(tǒng)計學(xué)軟件進行分析。結(jié)果:1 MSI分型在散發(fā)性CRC中的分布:其中MSI-H、MSI-L和MSS在散發(fā)性CRC的發(fā)生率分別為9.6%、1.6%和88.8%。2不同MSI分型的CRC具有獨特的臨床病理特征:右半結(jié)直腸癌患者、年輕患者中MSI-H發(fā)生率較高(P0.001);在MSI-H患者中低分化比例較高(P0.001),粘液腺癌比例較高(P0.001),不易出現(xiàn)神經(jīng)受侵(P=0.008),而淋巴結(jié)轉(zhuǎn)移較少見(P0.001),術(shù)后患者TNM分期中I/II期所占比例較高(P0.001)。MSS/MSI-L CRC多發(fā)生在直腸,病理類型以腺癌多見,中分化類型較多。不同的MSI分型與腫瘤侵及深度、脈管瘤栓、遠處轉(zhuǎn)移及性別等無關(guān)。3 KRAS基因在CRC的突變率為39.2%,12號密碼子與13密碼子的突變率分別為30.1%和8.3%,最常見的突變位點是12密碼子的p.G12D,突變率為14.7%(109/743),其次是13密碼子的p.G13D,突變率為7.9%。4 KRAS基因突變在CRC中的臨床病理特征:KRAS基因突變在女性患者中發(fā)生率較高44.4%(132/297),明顯高于男性的35.7%(159/446),P=0.014,差異有統(tǒng)計學(xué)意義;易出現(xiàn)粘液腺癌53.8%(84/156),P0.001;KRAS基因突變與年齡、腫瘤原發(fā)位置、分化程度、侵及深度、脈管瘤栓、神經(jīng)受侵、淋巴結(jié)轉(zhuǎn)移、遠處轉(zhuǎn)移等臨床病理特征沒有明顯的統(tǒng)計學(xué)意義(P0.05)。5 KRAS基因在MSI CRC與MSS/MSI-L CRC的突變率沒有統(tǒng)計學(xué)差異。KRAS基因12密碼子在MSS CRC的突變率高于MSI CRC,而13密碼子在MSI CRC的突變率比在MSS CRC的突變率高,差異有統(tǒng)計學(xué)意義。6以KRAS基因突變、MSI分型將CRC患者分組,不同分組間臨床病理特征的差異。KRAS基因突變型患者中粘液腺癌比例較高,女性患者KRAS基因突變率較高,差異均有統(tǒng)計學(xué)意義,而在MSI-H、KRAS基因突變型患者中,KRAS基因突變與性別、病理類型無統(tǒng)計學(xué)意義。MSI-H患者分化程度中低分化比例較高,神經(jīng)受侵比例低,而在KRAS基因突變型患者中,MSI分型與分化程度無統(tǒng)計學(xué)意義,KRAS基因野生型患者中,MSI分型與神經(jīng)受侵無關(guān)。KRAS基因突變與神經(jīng)受侵無統(tǒng)計學(xué)意義,但在MSS患者中,KRAS基因突變患者神經(jīng)受侵比率較高,差異有統(tǒng)計學(xué)意義。結(jié)論:1 MSI-H在散發(fā)性CRC的發(fā)生率為9.6%。不同MSI分型的CRC具有獨特的臨床病理特征。MSI-H患者多見于年輕患者,右半結(jié)腸多見,分化程度較低,易出現(xiàn)粘液腺癌,神經(jīng)受侵少見,淋巴結(jié)轉(zhuǎn)移少見,I/II期所占比例較高。2 KRAS基因在CRC的突變率為39.2%。KRAS基因突變與性別、病理類型等病理特征有關(guān),KRAS基因突變型患者女性多見,以粘液腺癌為主。3 KRAS基因在MSI CRC與MSS CRC的突變率沒有統(tǒng)計學(xué)差異,在不同的MSI分型中,12密碼子、13密碼子在KRAS基因突變型中的比例不同。KRAS基因12密碼子在MSS CRC的突變率高于MSI CRC,而13密碼子在MSI CRC的突變率比在MSS CRC的突變率高,差異有統(tǒng)計學(xué)意義。4以KRAS基因突變、MSI分型將CRC患者分組,不同分組間臨床病理特征存在差異。在MSI-H患者中,KRAS基因突變與性別、病理類型無關(guān);在KRAS基因突變型患者中,MSI分型與分化程度無關(guān);在KRAS基因野生型患者中,MSI分型與神經(jīng)受侵無關(guān);在MSS患者中,KRAS基因突變型患者神經(jīng)受侵比率較高。
[Abstract]:Objective: to analyze the clinicopathological features of MSI-H CRC and MSI-L/MSS CRC by detecting the expression of MMR protein in sporadic CRC, and to detect the mutation rate of KRAS gene at CRC under the premise of MSI typing, and to analyze the correlation between the KRAS gene and the MSI classification. Wild type MSS/MSI-L, B group KRAS gene wild type MSI-H, C group KRAS gene mutant MSS/MSI-L, D group KRAS gene mutation MSI-H four group, analysis the difference between different groups of clinicopathological features. Methods: randomly selected 743 cases of patients who were treated by CRC surgical resection from February 2015 to December 2016, excluding hereditary adenomatous polyposis, and the elimination of hereditary adenomatous polyposis. The patients of Lynch's syndrome were used to borrow the patient's related case data in our hospital medical record room, collect the basic information and clinical data of the patients. The results of KRAS gene detection after operation, the expression of MMR protein (MLH1, MSH2, MSH6 and PMS2) were detected by immunohistochemical method and the data were collected. The results were analyzed by SPSS 20 statistics software. The distribution of 1 MSI typing in sporadic CRC: the incidence of MSI-H, MSI-L and MSS in sporadic CRC was 9.6%, respectively, and CRC with different MSI types in 1.6% and 88.8%.2 had unique clinicopathological features: the incidence of MSI-H was higher in the right half of the colorectal cancer patients (P0.001); the low differentiation ratio in the MSI-H patients was higher in the mucous gland. The proportion of cancer is high (P0.001), and it is not easy to have nerve invasion (P=0.008), but lymph node metastasis is rare (P0.001). The proportion of I/II stage in TNM staging is higher (P0.001), and.MSS/MSI-L CRC occurs more in the rectum. The pathological types are common in adenocarcinoma and many types of differentiation. Different MSI typing and tumor invasion depth, vascular tumor thrombus, distant metastasis The mutation rate of the.3 KRAS gene in CRC was 39.2%, the mutation rate of No. 12 codon and 13 codon was 30.1% and 8.3% respectively. The most common mutation site was the p.G12D of the 12 codon, the mutation rate was 14.7% (109/743), followed by the p.G13D of the 13 cipher, the mutation rate was the clinicopathological feature of the 7.9%.4 KRAS gene mutation in CRC: KRAS base The incidence of mutation in women was 44.4% (132/297), which was significantly higher than that of male 35.7% (159/446) and P=0.014, and the difference was statistically significant; it was easy to occur mucous adenocarcinoma 53.8% (84/156), P0.001; KRAS gene mutation and age, primary location of tumor, degree of differentiation, invasion and depth, vascular tumor thrombus, nerve invasion, lymph node metastasis, distant metastasis, etc. There was no significant statistical significance (P0.05) the mutation rate of the.5 KRAS gene at MSI CRC and MSS/MSI-L CRC was not statistically significant. The mutation rate of the.KRAS gene 12 codon in MSS CRC was higher than that of MSI CRC, while the mutation rate of the 13 codon was higher than that of the.KRAS. The group of CRC patients, the difference of clinicopathological features between different groups, the proportion of mucous adenocarcinoma in the patients with.KRAS gene mutation is higher, and the mutation rate of KRAS gene is higher in female patients and the difference is statistically significant. In MSI-H and KRAS gene mutation patients, there is no difference between KRAS gene mutation and sex and the pathological type of.MSI-H patients with no statistical significance. The proportion of the degree of low differentiation is high and the proportion of the nerve invasion is low. In the patients with KRAS gene mutation, there is no significant difference in MSI typing and differentiation. In the KRAS gene wild-type patients, there is no statistically significant difference between the.KRAS gene mutation and the nerve invasion of the MSI genotyping and the nerve invasion, but in the MSS patients, the KRAS gene mutations have the nerve invasion ratio in the patients with the KRAS gene. Conclusion: the incidence of 1 MSI-H in the incidence of sporadic CRC is 9.6%. different MSI type CRC has unique clinicopathological features,.MSI-H patients are often seen in young patients, the right hemicon is more common, the degree of differentiation is low, the mucous adenocarcinoma is easy to appear, the nerve invasion is rare, the lymph node metastases are rare, the proportion of I/II period is higher. The mutation rate of the 2 KRAS gene in CRC is related to the pathological features of the 39.2%.KRAS gene mutation, sex and pathological type. The KRAS mutant patients are more common, and there is no statistical difference between the.3 KRAS gene of the mucous adenocarcinoma and the MSI CRC and MSS CRC. In the different MSI classification, the 12 codon and the 13 codon are in the KRAS gene mutation type. The mutation rate of.KRAS gene 12 codon 12 in MSS CRC was higher than that of MSI CRC, while the mutation rate of the 13 codon in MSI CRC was higher than that of MSS CRC, and the difference was statistically significant in.4 with KRAS gene mutation. The MSI classification was divided into groups and the clinicopathological characteristics were different between different groups. In the KRAS gene mutant patients, the MSI typing is not related to the degree of differentiation; in the KRAS gene wild-type patients, the MSI typing is not related to the invasion of the nerve; in the patients with MSS, the KRAS gene mutant patients have a higher rate of nerve invasion.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R735.34

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