發(fā)布時間：2018-09-01 12:11

【摘要】：[目的]通過免疫組化的方法在無轉(zhuǎn)移的肺腺癌原發(fā)灶組織及肺腺癌骨轉(zhuǎn)移病灶組織中檢測P62蛋白的表達(dá)水平。分析P62蛋白的表達(dá)高低與影像學(xué)表現(xiàn)及預(yù)后的關(guān)系,評價P62蛋白是否可作為臨床指導(dǎo)肺腺癌骨轉(zhuǎn)移預(yù)后的指標(biāo)。分析P62蛋白與經(jīng)典自噬底物L(fēng)C3的關(guān)系,初步探討P62蛋白是否通過自噬來參與肺腺癌骨轉(zhuǎn)移的過程。[方法]1、收集在2007年12月-2014年9月之間就診于昆明醫(yī)科大學(xué)第三附屬醫(yī)院并且行手術(shù)治療的肺腺癌骨轉(zhuǎn)移患者62例及無轉(zhuǎn)移的肺腺癌患者40例。采用免疫組織化學(xué)的方法,分別檢測無轉(zhuǎn)移組及肺腺癌骨轉(zhuǎn)移組中P62蛋白及LC3Ⅱ蛋白在術(shù)后石蠟切片中的表達(dá)情況,并分析二者表達(dá)水平有無差異性。2、于62例肺腺癌骨轉(zhuǎn)移組患者中檢測P62及LC3Ⅱ蛋白在術(shù)后石蠟切片的表達(dá)情況并分析P62蛋白及LC3Ⅱ蛋白的表達(dá)水平與臨床骨轉(zhuǎn)移病灶的個數(shù)、病理性骨折等相關(guān)因素的關(guān)系,分析與病灶無進(jìn)展生存時間的關(guān)系。分析在人肺腺癌骨轉(zhuǎn)移組織中P62蛋白及LC3Ⅱ蛋白表達(dá)水平的相關(guān)性,采用Log Rank檢驗通過分析P62蛋白的表達(dá)與骨病灶無進(jìn)展生存期及總生存期的關(guān)系來明確P62蛋白能否作為預(yù)測肺腺癌骨轉(zhuǎn)移臨床預(yù)后的指標(biāo)。應(yīng)用SPSS16. 0統(tǒng)計分析軟件進(jìn)行結(jié)果的統(tǒng)計分析(P0. 05有統(tǒng)計學(xué)意義)。[結(jié)果]1、在40例無轉(zhuǎn)移肺腺癌組中免疫組化結(jié)果顯示均有P62蛋白及LC3Ⅱ蛋白的表達(dá),表達(dá)位置主要為胞漿;免疫組化結(jié)果顯示P62蛋白以及LC3Ⅱ蛋白在62例肺腺癌骨轉(zhuǎn)移組中在胞漿及胞核中均有表達(dá)。P62蛋白在無轉(zhuǎn)移肺腺癌組的40例石蠟標(biāo)本中高表達(dá)的有18例,低表達(dá)的有22例;在肺腺癌骨轉(zhuǎn)移組中P62蛋白高表達(dá)的有40例,低表達(dá)的有22例。經(jīng)統(tǒng)計分析后發(fā)現(xiàn)這兩組中的P62蛋白表達(dá)水平差異有統(tǒng)計學(xué)意義(P=0.013)。LC3Ⅱ蛋白在無轉(zhuǎn)移肺腺癌組中高表達(dá)的有10例,低表達(dá)的有30例。而LC3Ⅱ蛋白在肺腺癌骨轉(zhuǎn)移組中高表達(dá)的有23例,低表達(dá)的有39例。統(tǒng)計分析后發(fā)現(xiàn)在這兩種不同組織中的LC3Ⅱ蛋白表達(dá)水平差異無統(tǒng)計學(xué)意義(P=0.145)。2、在肺腺癌骨轉(zhuǎn)移組中P62蛋白在不同性別、年齡、有無病理性骨折中無明顯差異,但在不同骨轉(zhuǎn)移個數(shù)中表達(dá)有差異,在三個或以上較三個及以下骨轉(zhuǎn)移患者P62表達(dá)增高(P=0.014)。在肺腺癌骨轉(zhuǎn)移組中P62蛋白低表達(dá)組的骨病灶無進(jìn)展中位生存期為9個月,P62蛋白高表達(dá)組的骨病灶無進(jìn)展中位生存期為5個月,兩組之間骨病灶無進(jìn)展生存期的差異有統(tǒng)計學(xué)意義(P=0.048)。在肺腺癌骨轉(zhuǎn)移組中LC3Ⅱ蛋白低表達(dá)組的骨病灶無進(jìn)展中位生存期為7個月,LC3Ⅱ蛋白高表達(dá)組的骨病灶無進(jìn)展中位生存期為5個月,兩組之間骨病灶無進(jìn)展生存期的差異無統(tǒng)計學(xué)意義(P=0.208)。3、肺腺癌骨轉(zhuǎn)移組中P62低表達(dá)組的中位生存期為12個月,高表達(dá)組的中位生存期為6個月,兩組之間的生存期差異有統(tǒng)計學(xué)意義(P=0.003)。LC3Ⅱ低表達(dá)組的中位生存期為12個月,高表達(dá)組的中位生存期為6個月,經(jīng)檢驗兩組之間的差異無統(tǒng)計學(xué)意義(P=0.074)。4、在肺腺癌骨轉(zhuǎn)移組織石蠟標(biāo)本中P62蛋白與LC3Ⅱ蛋白的表達(dá)水平未見明顯的相關(guān)性(P=0.703)。5、收集4例均有肺、淋巴結(jié)及骨病灶手術(shù)史的患者并檢測3種組織中P62蛋白的表達(dá)情況。結(jié)果顯示P62蛋白在肺部原發(fā)灶及淋巴結(jié)轉(zhuǎn)移灶,骨轉(zhuǎn)移灶中均有表達(dá),且免疫組化表達(dá)評分按肺部-淋巴結(jié)-骨的順序,有上升的趨勢。[結(jié)論]1. P62蛋白在肺腺癌骨轉(zhuǎn)移組織中的表達(dá)較無轉(zhuǎn)移的肺腺癌組織中明顯增高,表明P62蛋白的異常表達(dá)與肺腺癌轉(zhuǎn)移過程可能有關(guān);2. P62蛋白在肺腺癌骨轉(zhuǎn)移組織中表達(dá)水平與年齡、性別、有無病理性骨折均無關(guān)聯(lián),與骨轉(zhuǎn)移灶的個數(shù)成正相關(guān);3. P62蛋白的表達(dá)水平與肺腺癌骨轉(zhuǎn)移患者的無進(jìn)展生存期有關(guān),P62蛋白水平越高,骨轉(zhuǎn)移患者無進(jìn)展生存期越短;4. P62蛋白的表達(dá)水平與肺腺癌骨轉(zhuǎn)移患者的生存時間有關(guān),P62蛋白水平越高,肺腺癌骨轉(zhuǎn)移患者的生存時間越短;P62蛋白可能是影響肺腺癌骨轉(zhuǎn)移患者生存時間的獨(dú)立預(yù)后因素;5. P62蛋白與LC3蛋白表達(dá)無明顯相關(guān)性,提示P62可能不是通過自噬途徑調(diào)控肺腺癌骨轉(zhuǎn)移。
[Abstract]:[Objective] To detect the expression of P62 protein in non-metastatic lung adenocarcinoma and bone metastasis of lung adenocarcinoma by immunohistochemistry. To analyze the relationship between the expression of P62 protein and imaging manifestations and prognosis, and to evaluate whether P62 protein can be used as a prognostic indicator of bone metastasis of lung adenocarcinoma. [Methods] 1. 62 patients with bone metastasis from lung adenocarcinoma and 40 patients without metastasis were collected from the Third Affiliated Hospital of Kunming Medical University between December 2007 and September 2014. Immunohistochemistry was used to detect the expression of P62 protein and LC3II protein in paraffin sections of non-metastasis group and lung adenocarcinoma bone metastasis group, and to analyze the difference between them. 2. The expression of P62 and LC3II protein in paraffin sections of 62 patients with lung adenocarcinoma bone metastasis was detected and analyzed. The correlation between the expression levels of protein P62 and LC3II in human lung adenocarcinoma with bone metastasis was analyzed by Log Rank test. The relationship between progression-free survival and total survival of bone lesions was used to determine whether P62 protein could be used as a predictor of clinical prognosis of lung adenocarcinoma with bone metastasis. C3II protein was mainly expressed in cytoplasm; immunohistochemistry showed that P62 protein and LC3II protein were both expressed in the cytoplasm and nucleus of 62 cases of lung adenocarcinoma with bone metastasis. P62 protein was overexpressed in 18 cases of paraffin specimens from 40 cases of non-metastatic lung adenocarcinoma, and underexpressed in 22 cases of lung adenocarcinoma with bone metastasis. The expression of P62 protein was significantly different between the two groups (P=0.013). LC3 II protein was overexpressed in 10 cases of non-metastatic lung adenocarcinoma and underexpressed in 30 cases. LC3 II protein was overexpressed in 23 cases of lung adenocarcinoma with bone metastasis and underexpressed in 3 cases of lung adenocarcinoma with bone metastasis. There was no significant difference in the expression of LC3 II protein between the two tissues (P = 0.145). In the bone metastasis group of lung adenocarcinoma, there was no significant difference in the expression of P62 protein between the sexes, ages and pathological fractures, but there were differences in the number of bone metastases, and there were differences in the expression of P62 protein among three or more bone metastases. The median progression-free survival time of bone lesions was 9 months in the group with low expression of P62 protein and 5 months in the group with high expression of P62 protein. The median progression-free survival time of bone lesions was 7 months in the low expression group, 5 months in the high expression group and 12 months in the low expression group. The median survival time of the high expression group was 6 months, and the difference between the two groups was statistically significant (P = 0.003). The median survival time of the low expression group was 12 months, and that of the high expression group was 6 months. There was no significant difference between the two groups (P = 0.074). There was no significant correlation between the expression of P62 protein and the level of LC3 II protein (P=0.703). The expression of P62 protein in bone metastasis tissues of lung adenocarcinoma was significantly higher than that in non-metastasis tissues of lung adenocarcinoma, indicating that the abnormal expression of P62 protein may be related to the metastasis process of lung adenocarcinoma. 2. The expression level of P62 protein in bone metastasis tissues of lung adenocarcinoma was related to age, sex and pathology. The expression level of P62 protein was related to the progression-free survival of patients with bone metastasis of lung adenocarcinoma. The higher the level of P62 protein, the shorter the progression-free survival of patients with bone metastasis. 4. The expression level of P62 protein was related to the survival time of patients with bone metastasis of lung adenocarcinoma. P62 protein may be an independent prognostic factor affecting the survival time of lung adenocarcinoma patients with bone metastasis. 5. P62 protein has no significant correlation with the expression of LC3 protein, suggesting that P62 may not regulate bone metastasis of lung adenocarcinoma through autophagy.
【學(xué)位授予單位】：昆明醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R734.2

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