结直肠癌BRAF及PIK3CA基因突变的检测及意义

发布时间：2018-04-01 23:35

本文选题：结直肠癌　切入点：KRAS　出处：《青岛大学》2017年硕士论文

【摘要】：目的:1.检测结直肠癌患者中的KRAS、BRAF及PIK3CA出现突变的情况;2.检测结直肠癌MSI表达的情况;3.探讨结直肠癌组织中的KRAS、BRAF及PIK3CA突变情况与相应的临床病理之间的联系;4.探究MSI表达与临床病理特征的关系;5.分析结直肠癌组织中KRAS、BRAF与PIK3CA突变的相关临床意义;6.分析结直肠癌组织中MSI表达所具有的临床意义。方法:选取2014年1月至2016年1月就诊于我院普外科并行结直肠癌根治术的患者125例。提取DNA经PCR扩增后,检测KRAS、BRAF及PIK3CA突变情况,同时行免疫组化,观察MSI表达的情况,分析结直肠癌组织中KRAS、BRAF、PIK3CA突变情况及MSI表达情况与结直肠癌临床病理学的相关性。结果:125例患者由73名男性患者与52名女性患者组成,分别占58.4%与41.6%,年龄区间为29-89岁(63.6±11.46)。125例患者中,发生KRAS突变的患者有46例(36.8%);BRAF基因发生突变的患者3例(2.4%);PIK3CA基因发生突变的患者2例(1.6%);MSI存在56例(44.8%)。MSI与MSH2、MSH6跟肿瘤类型具有相关性(P=0.031、P=0.001、P=0.046),MSI与MLH1跟肿瘤分化程度具有相关性(P=0.005、P=0.004),其他组别的P值均0.05。结论:1.KRAS、BRAF、PIK3CA基因突变情况在结直肠癌患者中存在,但表现情况各不相同并相互独立,且与临床病理特征之间无明显关系,无法直接通过临床病理特征的情况直接判断结直肠癌患者能否从抗EGRE治疗中获益,故进行抗EGFR治疗前仍需进行相关基因的检测。2.MSI表达情况与临床病理特征之间存在一定联系,但各修复蛋白表达情况相互独立,且与KRAS、BRAF、PIK3CA基因突变情况无相关性,同样无发通过临床病理特征的情况直接判断结直肠癌患者预后情况。
[Abstract]:Objective\\\. The relationship between MSI expression and clinicopathological features 5. To analyze the correlation between PIK3CA mutation and KRASA BRAF mutation in colorectal cancer. 6. To analyze the clinical significance of MSI expression in colorectal cancer tissues. Methods: from January 2014 to 2016 1, 1. DNA was extracted from 125 patients who underwent radical resection of colorectal cancer in our hospital. DNA was amplified by PCR. The mutation of BRAF and PIK3CA in KRASA was detected, and the expression of MSI was observed by immunohistochemistry. To analyze the relationship between the mutation of KRASA BRAFU PIK3CA, the expression of MSI and the clinicopathology of colorectal cancer. Results there were 73 male patients and 52 female patients, accounting for 58.4% and 41.6%, respectively. The age range was 29-89 years (63.6 卤11.46.125). There were 46 patients with KRAS mutation, including 3 patients with BRAF gene mutation, 2 patients with PIK3CA gene mutation and 56 patients with KRAS mutation. There was a correlation between MSI and MSH2MSH6 and tumor type (P0.031P0.001P0.046A). There was a correlation between P0.031MMSI and the degree of differentiation between MLH1 and tumor. Conclusion: 1. The mutation of BRAFK3CA gene in KRASA BRAFK3CA gene was found in patients with colorectal cancer. However, the manifestations were different and independent, and had no obvious relationship with the clinicopathological features. It was not possible to directly determine whether the patients with colorectal cancer could benefit from the anti- EGRE therapy through the clinicopathological features. Therefore, it is necessary to detect the related genes before anti-MSI therapy. 2. There is a certain relationship between the expression of EGFR and clinicopathological features, but the expression of each repair protein is independent of each other, and there is no correlation with the mutation of KRAS-BRAFU PIK3CA gene. Similarly, the prognosis of colorectal cancer patients was judged directly by clinicopathological features.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.34

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