KRAS基因与MSI在散发性结直肠癌的关联性研究

发布时间：2018-06-14 09:58

本文选题：结直肠癌 + KRAS基因　；参考：《河北医科大学》2017年硕士论文

【摘要】：目的:本课题主要通过检测MMR蛋白在散发性CRC中的表达情况,分析MSI-H CRC与MSI-L/MSS CRC的临床病理特征。在明确MSI分型的前提下,检测KRAS基因在CRC的突变率,分析其与MSI分型之间的关联性。以KRAS基因突变、MSI分型将CRC患者分为A组KRAS基因野生型MSS/MSI-L、B组KRAS基因野生型MSI-H、C组KRAS基因突变型MSS/MSI-L、D组KRAS基因突变型MSI-H四组,分析不同组间临床病理特征的差异。方法:随机选取2015年2月至2016年12月就诊于我院行CRC手术切除治疗的患者743例,排除遗传性腺瘤性息肉病和林奇综合征患者,于我院病案室借阅患者的相关病例资料,收集患者的基本信息及临床数据、患者术后KRAS基因检测结果,应用免疫组化法检测患者MMR蛋白(MLH1、MSH2、MSH6和PMS2)表达并收集资料,结果数据使用SPSS 20统计学软件进行分析。结果:1 MSI分型在散发性CRC中的分布:其中MSI-H、MSI-L和MSS在散发性CRC的发生率分别为9.6%、1.6%和88.8%。2不同MSI分型的CRC具有独特的临床病理特征:右半结直肠癌患者、年轻患者中MSI-H发生率较高(P0.001);在MSI-H患者中低分化比例较高(P0.001),粘液腺癌比例较高(P0.001),不易出现神经受侵(P=0.008),而淋巴结转移较少见(P0.001),术后患者TNM分期中I/II期所占比例较高(P0.001)。MSS/MSI-L CRC多发生在直肠,病理类型以腺癌多见,中分化类型较多。不同的MSI分型与肿瘤侵及深度、脉管瘤栓、远处转移及性别等无关。3 KRAS基因在CRC的突变率为39.2%,12号密码子与13密码子的突变率分别为30.1%和8.3%,最常见的突变位点是12密码子的p.G12D,突变率为14.7%(109/743),其次是13密码子的p.G13D,突变率为7.9%。4 KRAS基因突变在CRC中的临床病理特征:KRAS基因突变在女性患者中发生率较高44.4%(132/297),明显高于男性的35.7%(159/446),P=0.014,差异有统计学意义;易出现粘液腺癌53.8%(84/156),P0.001;KRAS基因突变与年龄、肿瘤原发位置、分化程度、侵及深度、脉管瘤栓、神经受侵、淋巴结转移、远处转移等临床病理特征没有明显的统计学意义(P0.05)。5 KRAS基因在MSI CRC与MSS/MSI-L CRC的突变率没有统计学差异。KRAS基因12密码子在MSS CRC的突变率高于MSI CRC,而13密码子在MSI CRC的突变率比在MSS CRC的突变率高,差异有统计学意义。6以KRAS基因突变、MSI分型将CRC患者分组,不同分组间临床病理特征的差异。KRAS基因突变型患者中粘液腺癌比例较高,女性患者KRAS基因突变率较高,差异均有统计学意义,而在MSI-H、KRAS基因突变型患者中,KRAS基因突变与性别、病理类型无统计学意义。MSI-H患者分化程度中低分化比例较高,神经受侵比例低,而在KRAS基因突变型患者中,MSI分型与分化程度无统计学意义,KRAS基因野生型患者中,MSI分型与神经受侵无关。KRAS基因突变与神经受侵无统计学意义,但在MSS患者中,KRAS基因突变患者神经受侵比率较高,差异有统计学意义。结论:1 MSI-H在散发性CRC的发生率为9.6%。不同MSI分型的CRC具有独特的临床病理特征。MSI-H患者多见于年轻患者,右半结肠多见,分化程度较低,易出现粘液腺癌,神经受侵少见,淋巴结转移少见,I/II期所占比例较高。2 KRAS基因在CRC的突变率为39.2%。KRAS基因突变与性别、病理类型等病理特征有关,KRAS基因突变型患者女性多见,以粘液腺癌为主。3 KRAS基因在MSI CRC与MSS CRC的突变率没有统计学差异,在不同的MSI分型中,12密码子、13密码子在KRAS基因突变型中的比例不同。KRAS基因12密码子在MSS CRC的突变率高于MSI CRC,而13密码子在MSI CRC的突变率比在MSS CRC的突变率高,差异有统计学意义。4以KRAS基因突变、MSI分型将CRC患者分组,不同分组间临床病理特征存在差异。在MSI-H患者中,KRAS基因突变与性别、病理类型无关;在KRAS基因突变型患者中,MSI分型与分化程度无关;在KRAS基因野生型患者中,MSI分型与神经受侵无关;在MSS患者中,KRAS基因突变型患者神经受侵比率较高。
[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.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.34

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