P62蛋白在人肺腺癌骨转移组织中的表达及临床意义

发布时间：2018-09-01 12:11

【摘要】：[目的]通过免疫组化的方法在无转移的肺腺癌原发灶组织及肺腺癌骨转移病灶组织中检测P62蛋白的表达水平。分析P62蛋白的表达高低与影像学表现及预后的关系,评价P62蛋白是否可作为临床指导肺腺癌骨转移预后的指标。分析P62蛋白与经典自噬底物LC3的关系,初步探讨P62蛋白是否通过自噬来参与肺腺癌骨转移的过程。[方法]1、收集在2007年12月-2014年9月之间就诊于昆明医科大学第三附属医院并且行手术治疗的肺腺癌骨转移患者62例及无转移的肺腺癌患者40例。采用免疫组织化学的方法,分别检测无转移组及肺腺癌骨转移组中P62蛋白及LC3Ⅱ蛋白在术后石蜡切片中的表达情况,并分析二者表达水平有无差异性。2、于62例肺腺癌骨转移组患者中检测P62及LC3Ⅱ蛋白在术后石蜡切片的表达情况并分析P62蛋白及LC3Ⅱ蛋白的表达水平与临床骨转移病灶的个数、病理性骨折等相关因素的关系,分析与病灶无进展生存时间的关系。分析在人肺腺癌骨转移组织中P62蛋白及LC3Ⅱ蛋白表达水平的相关性,采用Log Rank检验通过分析P62蛋白的表达与骨病灶无进展生存期及总生存期的关系来明确P62蛋白能否作为预测肺腺癌骨转移临床预后的指标。应用SPSS16. 0统计分析软件进行结果的统计分析(P0. 05有统计学意义)。[结果]1、在40例无转移肺腺癌组中免疫组化结果显示均有P62蛋白及LC3Ⅱ蛋白的表达,表达位置主要为胞浆;免疫组化结果显示P62蛋白以及LC3Ⅱ蛋白在62例肺腺癌骨转移组中在胞浆及胞核中均有表达。P62蛋白在无转移肺腺癌组的40例石蜡标本中高表达的有18例,低表达的有22例;在肺腺癌骨转移组中P62蛋白高表达的有40例,低表达的有22例。经统计分析后发现这两组中的P62蛋白表达水平差异有统计学意义(P=0.013)。LC3Ⅱ蛋白在无转移肺腺癌组中高表达的有10例,低表达的有30例。而LC3Ⅱ蛋白在肺腺癌骨转移组中高表达的有23例,低表达的有39例。统计分析后发现在这两种不同组织中的LC3Ⅱ蛋白表达水平差异无统计学意义(P=0.145)。2、在肺腺癌骨转移组中P62蛋白在不同性别、年龄、有无病理性骨折中无明显差异,但在不同骨转移个数中表达有差异,在三个或以上较三个及以下骨转移患者P62表达增高(P=0.014)。在肺腺癌骨转移组中P62蛋白低表达组的骨病灶无进展中位生存期为9个月,P62蛋白高表达组的骨病灶无进展中位生存期为5个月,两组之间骨病灶无进展生存期的差异有统计学意义(P=0.048)。在肺腺癌骨转移组中LC3Ⅱ蛋白低表达组的骨病灶无进展中位生存期为7个月,LC3Ⅱ蛋白高表达组的骨病灶无进展中位生存期为5个月,两组之间骨病灶无进展生存期的差异无统计学意义(P=0.208)。3、肺腺癌骨转移组中P62低表达组的中位生存期为12个月,高表达组的中位生存期为6个月,两组之间的生存期差异有统计学意义(P=0.003)。LC3Ⅱ低表达组的中位生存期为12个月,高表达组的中位生存期为6个月,经检验两组之间的差异无统计学意义(P=0.074)。4、在肺腺癌骨转移组织石蜡标本中P62蛋白与LC3Ⅱ蛋白的表达水平未见明显的相关性(P=0.703)。5、收集4例均有肺、淋巴结及骨病灶手术史的患者并检测3种组织中P62蛋白的表达情况。结果显示P62蛋白在肺部原发灶及淋巴结转移灶,骨转移灶中均有表达,且免疫组化表达评分按肺部-淋巴结-骨的顺序,有上升的趋势。[结论]1. P62蛋白在肺腺癌骨转移组织中的表达较无转移的肺腺癌组织中明显增高,表明P62蛋白的异常表达与肺腺癌转移过程可能有关;2. P62蛋白在肺腺癌骨转移组织中表达水平与年龄、性别、有无病理性骨折均无关联,与骨转移灶的个数成正相关;3. P62蛋白的表达水平与肺腺癌骨转移患者的无进展生存期有关,P62蛋白水平越高,骨转移患者无进展生存期越短;4. P62蛋白的表达水平与肺腺癌骨转移患者的生存时间有关,P62蛋白水平越高,肺腺癌骨转移患者的生存时间越短;P62蛋白可能是影响肺腺癌骨转移患者生存时间的独立预后因素;5. P62蛋白与LC3蛋白表达无明显相关性,提示P62可能不是通过自噬途径调控肺腺癌骨转移。
[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.
【学位授予单位】：昆明医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2

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