Spartin蛋白在食管胃交界腺癌中的表达及意义

发布时间：2018-03-10 09:51

本文选题：食管胃交界腺癌　切入点：SPG20　出处：《河北医科大学》2015年硕士论文　论文类型：学位论文

【摘要】：目的:食管胃交界腺癌(adenocarcinoma of esophagogastric junction,AEGJ)是发生于食管与胃交界区域内,侵及食管胃交界(齿状线)的腺癌。手术是治疗食管胃交界腺癌的主要治疗方式,但术后肿瘤复发及淋巴结转移是增加其死亡率的一项重要原因,其根治术后5年生存率仍不足30%,而且在近十几年来并无显著改善,较早出现淋巴结转移、预后差是食管胃交界腺癌的重要生物学特征,但其原因及机制目前仍不清楚。既往研究证实,能够编码Spartin蛋白的SPG 20基因的甲基化在结直肠癌中水平较高,导致Spartin蛋白的低表达,而正常的粘膜组织Spartin蛋白表达水平较高。因此,Spartin蛋白可能成为腺癌的分子标志物和致癌机制之一。本文旨在通过观察Spartin蛋白在食管胃交界腺癌中的表达水平,探讨其与食管为交界腺癌发生、发展之间的关系,为食管胃交界腺癌发生的机制提供新的研究方向。方法:标本取自河北医科大学第四医院2013年10月-2014年02月期间行手术治疗的60例食管胃交界腺癌患者,其中男40例,女20例;年龄46~72岁,平均(54.5±6.9)岁。所有标本经HE染色病理证实为腺癌。手术切除标本0.5 h内取新鲜癌组织、正常粘膜组织。福尔马林固定,石蜡包埋,制作石蜡切片,用于免疫组织化学染色。应用免疫组织化学SP法分别检测60份标本癌组织及正常粘膜组织中Spartin蛋白的表达情况。应用彩色病理图像分析系统在高倍镜下测定免疫组化结果。所得试验数据通过SPSS 16.0统计软件进行处理,两组比较采用t检验,计量资料采用平均数±标准差,计数资料采用χ2检验比较各指标的相互关系。P0.05表示差异有统计学意义。结果:1全部60例食管胃交界腺癌组织中,其中23例Spartin蛋白表达呈阳性,阳性表达率为38.33%;食管胃交界腺癌患者正常粘膜组织组织60例,其中50例Spartin基因蛋白表达呈阳性,阳性表达率为83.33%,食管胃交界腺癌患者正常粘膜组织Spartin蛋白阳性表达率显著高于癌组织(P0.01);2 Spartin蛋白水平随临床分期增高、分化程度降低及发生淋巴结转移而明显降低,不同分期之间比较具有显著差异(χ2=9.212,P=0.018),不同分化程度比较有显著性差异(χ2=12.564,P=0.011),有淋巴结转移患者Spartin蛋白水平较低(χ2=9.414,P0.005)。Spartin蛋白水平与食管胃交界腺癌患者的性别、年龄、分化程度、肿瘤大小、组织分型及浸润深度无关(P0.05);3全部60例食管胃交界腺癌参与术后随访,随访时间为16个月以上,观察术后吻合口局部复发情况,纵隔、腹腔淋巴结转移及远处转移情况。术后16个月无进展生存者46例,肿瘤进展者14例,其中吻合口复发1例,纵隔、腹腔淋巴结转移5例,远处转移9例(1例为纵隔淋巴结及肝多发转移);4随访的60例患者,23例癌组织Spartin蛋白阳性表达者术后16个月发生复发转移4例,16个月无进展生存率为82.61%;Spartin蛋白阴性表达者37例,观察至术后16个月出现复发转移10例,16个月无进展生存率为72.93%;5对肿瘤大小、分化程度、浸润深度、淋巴结转移、临床分期和Spartin蛋白表达等临床病理因素采用COX多因素分析,结果表明食管胃交界腺癌患者分化程度、临床分期、浸润深度和Spartin蛋白表达可以作为独立预测因子,浸润深度增加,患者复发转移风险增大(风险度=4.561,P=0.032),腺癌分化程度越低,患者复发转移风险也越高(风险度=5.620,P=0.017),临床分期的越高,患者复发转移风险增大(风险度=5.254,P=0.021),患者出现淋巴结转移,患者复发转移风险增大(风险度=3.998,P=0.045);Spartin蛋白表达低,患者复发转移风险增大(风险度=2.998,P=0.025)。结论:1 Spartin蛋白在食管胃交界腺癌组织中低表达,与正常粘膜组织有显著性差异,提示Spartin蛋白缺失表达可能在食管胃交界腺癌发生过程中具有重要作用,可能与食管胃交界腺癌的发生、发展有关;2食管胃交界腺癌患者癌组织中Spartin蛋白表达水平与临床分期、分化程度及是否有淋巴结转移有关;3 Spartin蛋白表达异常者具有明显的术后复发、转移风险,提示Spartin蛋白表达可能成为食管胃交界腺癌预后预测因子。
[Abstract]:Objective: gastroesophageal junction adenocarcinoma (adenocarcinoma of esophagogastric junction, AEGJ) occurred in the esophagus and gastric junction area, at the junction of invasion of esophageal and gastric adenocarcinoma (dentate line). Surgery is the main treatment of adenocarcinoma of the esophagogastric junction, but the postoperative tumor recurrence and lymph node metastasis is a an important reason for its mortality, the radical postoperative 5 years survival rate is still less than 30%, and there is no significant improvement in the past ten years earlier, lymph node metastasis, poor prognosis is an important biological feature of gastroesophageal junction adenocarcinoma, but its causes and mechanism are still unclear. The previous studies showed that methylation can encoding Spartin SPG protein 20 gene level in colorectal cancer, leading to low expression of Spartin protein in normal gastric mucosa, and the expression level of Spartin protein is higher. Therefore, Spartin protein may be molecular for adenocarcinoma of the subject One of the markers and carcinogenic mechanism. This paper aims at the expression level of junction carcinoma in esophagus and stomach through the observation of Spartin protein, and to evaluate the esophagus junction adenocarcinoma, relationship between development, provide a new research direction for the esophagogastric junction adenocarcinoma mechanism. Methods: the samples were taken from the fourth hospital of Hebei Medical University during -2014 October 2013 in 02 months in 60 cases of surgical treatment of gastroesophageal junction adenocarcinoma patients, 40 were male, 20 were female; aged 46~72 years old, the average (54.5 + 6.9) years old. All specimens were confirmed by HE staining for adenocarcinoma. Surgical specimens within 0.5 h from the fresh cancer tissue and normal mucosa of formalin. Fixed, paraffin, paraffin sections were used for immunohistochemical staining. The expression of Spartin protein were detected in 60 specimens of carcinoma and normal mucosa tissues by SP immunohistochemical method. By pathological color Analysis system for determination of immune group at high magnification of the image. The experimental data were processed by statistical software SPSS 16, the two groups were compared with t test, measurement data with the average standard deviation, count data using 2 test comparison of each index between.P0.05 table was statistically significant difference. The results shows: the junction 1 of all the 60 patients with esophageal and gastric adenocarcinoma, including 23 cases of Spartin protein expression was positive, the positive rate was 38.33%; adenocarcinoma of the esophagogastric junction patients with normal mucosa tissue in 60 cases, including 50 cases of Spartin gene protein expression was positive, the positive rate was 83.33%, the positive expression of Spartin protein in esophageal gastric junction adenocarcinoma in patients with normal mucosa tissues was significantly higher than that in cancer tissue (P0.01); 2 Spartin protein level increased with the clinical stage, degree of differentiation and reduce the occurrence of lymph node metastasis decreased significantly with comparison between different stages. There were significant differences (2=9.212, P=0.018), different differentiation degree had significant difference (2=12.564, P=0.011), lymph node metastasis, Spartin protein levels were lower (2=9.414, P0.005).Spartin protein level and gastroesophageal junction adenocarcinoma patients with gender, age, differentiation degree, tumor size, histological the type and depth of invasion (P0.05); followed up 3 of all 60 cases of adenocarcinoma of the esophagogastric junction in the postoperative follow-up time was 16 months, and local recurrence of mediastinal anastomosis, postoperative observation, lymph node metastasis and distant metastasis of abdominal cavity. After 16 months of progression free survival in 46 cases, 14 cases the tumor progression, including anastomotic recurrence in 1 cases, mediastinal and abdominal lymph node metastasis in 5 cases, 9 cases with distant metastases (1 cases of mediastinal lymph node and liver metastasis); 60 cases of 4 follow-up patients, 23 cases of positive expression of Spartin protein in cancer patients after 16 months of recurrence and metastasis 4 cases, 16 months of progression free survival rate was 82.61%; 37 cases of Spartin negative expression, to observe 16 months after surgery, recurrence and metastasis in 10 cases, 16 month progression free survival rate was 72.93%; 5 of the tumor size, degree of differentiation, depth of invasion, lymph node metastasis, clinical stage by multivariate analysis with COX and Spartin protein expression and other clinicopathological factors. The results show that the degree of differentiation of gastroesophageal junction adenocarcinoma patients, clinical stage, the expression can be used as independent predictors of the depth of invasion and Spartin protein, infiltration depth increased, with increased risk of recurrence (hazard ratio =4.561, P=0.032), the degree of differentiation of adenocarcinoma of the lower risk of recurrence and metastasis in patients (the higher the risk of =5.620, P=0.017), the higher clinical stage, recurrence and metastasis of patients with increased risk (risk =5.254, P=0.021), patients with lymph node metastasis, recurrence and metastasis in patients with increased risk (the risk of =3.998, P=0.045, Sparti); The low expression of N protein in patients with increased risk of recurrence and metastasis (hazard ratio =2.998, P=0.025). Conclusion: the low expression of Spartin protein at the junction of 1 adenocarcinoma in esophagus and stomach, and there was significant difference compared with normal mucosa, suggesting that loss of Spartin protein expression may play an important role in the occurrence of gastroesophageal junction adenocarcinoma and esophageal process gastric junction adenocarcinoma, development; 2 esophagogastric junction cancer tissues of patients with adenocarcinoma of the expression level of Spartin protein and clinical stage, degree of differentiation and lymph node metastasis; 3 Spartin protein abnormal expression with recurrence, obvious postoperative metastasis risk, suggesting that Spartin protein expression may become esophagogastricjunction prognosis adenocarcinoma predictors.

【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R735

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