本文選題：結(jié)直腸癌　切入點：KRAS　出處：《青島大學(xué)》2017年碩士論文

【摘要】：目的:1.檢測結(jié)直腸癌患者中的KRAS、BRAF及PIK3CA出現(xiàn)突變的情況;2.檢測結(jié)直腸癌MSI表達(dá)的情況;3.探討結(jié)直腸癌組織中的KRAS、BRAF及PIK3CA突變情況與相應(yīng)的臨床病理之間的聯(lián)系;4.探究MSI表達(dá)與臨床病理特征的關(guān)系;5.分析結(jié)直腸癌組織中KRAS、BRAF與PIK3CA突變的相關(guān)臨床意義;6.分析結(jié)直腸癌組織中MSI表達(dá)所具有的臨床意義。方法:選取2014年1月至2016年1月就診于我院普外科并行結(jié)直腸癌根治術(shù)的患者125例。提取DNA經(jīng)PCR擴增后,檢測KRAS、BRAF及PIK3CA突變情況,同時行免疫組化,觀察MSI表達(dá)的情況,分析結(jié)直腸癌組織中KRAS、BRAF、PIK3CA突變情況及MSI表達(dá)情況與結(jié)直腸癌臨床病理學(xué)的相關(guān)性。結(jié)果:125例患者由73名男性患者與52名女性患者組成,分別占58.4%與41.6%,年齡區(qū)間為29-89歲(63.6±11.46)。125例患者中,發(fā)生KRAS突變的患者有46例(36.8%);BRAF基因發(fā)生突變的患者3例(2.4%);PIK3CA基因發(fā)生突變的患者2例(1.6%);MSI存在56例(44.8%)。MSI與MSH2、MSH6跟腫瘤類型具有相關(guān)性(P=0.031、P=0.001、P=0.046),MSI與MLH1跟腫瘤分化程度具有相關(guān)性(P=0.005、P=0.004),其他組別的P值均0.05。結(jié)論:1.KRAS、BRAF、PIK3CA基因突變情況在結(jié)直腸癌患者中存在,但表現(xiàn)情況各不相同并相互獨立,且與臨床病理特征之間無明顯關(guān)系,無法直接通過臨床病理特征的情況直接判斷結(jié)直腸癌患者能否從抗EGRE治療中獲益,故進行抗EGFR治療前仍需進行相關(guān)基因的檢測。2.MSI表達(dá)情況與臨床病理特征之間存在一定聯(lián)系,但各修復(fù)蛋白表達(dá)情況相互獨立,且與KRAS、BRAF、PIK3CA基因突變情況無相關(guān)性,同樣無發(fā)通過臨床病理特征的情況直接判斷結(jié)直腸癌患者預(yù)后情況。
[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 鹵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.
【學(xué)位授予單位】：青島大學(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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