【作者】 李建；

【导师】 胡国潢；

【作者基本信息】 中南大学 ， 普通外科学， 2011， 硕士

【摘要】 背景胰腺癌是所有实体肿瘤中预后最差的肿瘤之一,其中胰腺导管腺癌占胰腺癌的80%以上。胰腺癌总体5年生存率低于5%,中位生存期少于6个月。大部分病人被确诊时已属晚期,仅15%的患者在就诊时可行根治性手术,且术后复发率超过85%。虽然近年来胰腺癌诊断和治疗有了很大的进步,但胰腺癌的总体预后未见明显改善,严重威胁着人类的健康。胰腺癌的发生、发展、转移是多因素参与、多步骤的复杂过程,涉及遗传学和表观遗传学改变,而细胞的增殖和凋亡异常是肿瘤细胞永生性的常见原因。有人报道胰腺癌的早期可能有Survivin的表达,且主要在胰腺导管细胞癌中表达呈阳性,而在非肿瘤的胰腺组织中极少见表达,从而可视为胰腺癌发生的早期诊断指标和治疗靶点。近年来发现Psmd10是在肝癌发生过程中发挥重要作用的蛋白,而在胰腺导管腺癌组织表达情况罕见报道,故其对胰腺导管腺癌的诊断价值及治疗意义都有待进一步认识。目的检测Survivin和Psmd10蛋白在胰腺导管腺癌组织中的表达,探讨两者与胰腺导管腺癌临床病理特征及预后的关系、两者的相关性及二者的临床意义。方法应用免疫组织化学方法检测42例胰腺导管腺癌组织及10例正常胰腺组织中Survivin和Psmd10的表达。结果1. Survivin和Psmd10在胰腺导管腺癌组织中的表达均显著高于在正常胰腺组织中的表达(p<0.01),两者在胰腺导管腺癌组织中表达的阳性率分别为88.1%(37/42)和71.4%(30/42),且呈等级相关(R=0.448,P=0.003)；2. Survivin表达与胰腺导管腺癌分化程度呈正相关(P=0.018),与胰腺导管腺癌患者的性别、年龄、肿瘤部位、肿瘤大小及淋巴结转移与否不相关；Psmd10表达与胰腺导管腺癌分化程度呈正相关(P=0.001),与性别、年龄、肿瘤部位、肿瘤大小及淋巴结转移不相关。3. Survivin和Psmd10表达阳性与胰腺导管腺癌患者短的术后生存时间显著相关(p=0.023；p=0.107)结论1. Survivin、Psmd10可能与胰腺导管腺癌的发生发展有关。2. Survivin、Psmd10在胰腺导管腺癌发生发展中可能有协同作用。3. Survivin、Psmd10可以提示胰腺导管腺癌患者预后。更多还原

【Abstract】 BackgroundPancreatic cancer is one of the solid malgnancies with the worst prognosis,and pancreatic ductal adenocarcinoma account for more than 80% of pancreatic cancer.The five year survival rate of pancreatic cancer is below 5%,and its median survival time is less than 6 months.When diagnosed as pancreatic cancer,most patients are in the advanced stages, only about 15% patient can undergo radical surgery after being diagnosed,furthermore,the postoperative reccurence rate is more than85%. Despite the great improvements in diagnosis and clinic treatment,the overall prognosis for pancreatic cancer has not improved significantly.it posed a tremendous threat on people’s health. The occurrence, development and metastasis of pancreatic cancer is a complicated process involving in genetic and epigenetic change, and the abnormality of cellular proliferation and apoptosis are the common causes of the immortality of tumor cell.It is reported that the expression of Survivin might happen in the early stage of pancreatic cancer,moreover,it mainly expresses in pancreatic ductal adeno-carcinoma,whereas it is negative in the non-cancerous tissue,therefore,it can be regard as the early diagnosis indicator of tumor occurance and therapeutic target.Psmd10,detected in the precent years,plays a significant role in tumorigenesis in HCC.However, reports involving in the expression of Psmd10 in pancreatic ductal adenocarcinoma is rare.Therefore, its significance in diagnosis and treatment of pancreatic ductal adenocarcinoma need further study.ObjectiveTo investigate the expression of Survivin and Psmd10 in Human Pancreatic ductal adenocarcinoma tissues, analysis the relationship between expression of Survivin、Psmd10 and clinicopathological features and prognosis of pancreatic ductal adenocarcinoma and evaluate the clinical significances of Survivin and Psmd10.MethodsS-P immunohistochemical staining was performed to detect the expression of Survivin and Psmd10 in 42 human pancreatic ductal adenocarcinoma tissues and 10 normal pancreatic tissues.Results:1. The expressions of both Survivin and Psmd10 in human pancreatic ductal adenocarcinoma tissues were significantly higher than those of normal pancreatic tissues (p<0.01). The positive rate of Survivin and Psmd10 in 42 human pancreatic ductal adenocarcinoma tissues were 88.1%(37/42) and 71.4%(30/42) respectively, correlation between them were exist from ranks (R=0.448, P=0.003).2. There was direct correlation between expression of Survivin and differentiation of human pancreatic ductal adenocarcinoma (P=0.018), but no associated with the age, sex, tumor size, tumor location and lymph node metastasis. And there was direct correlation between expression of Psmd10 and differentiation of human pancreatic ductal adenocarcinoma (P=0.001), but no associated with the age, sex, tumor size, tumor location and lymph node metastasis.3.The positive expression of Survivin and Psmd10 in pancreatic ductal adenocarcinoma tissues were significantly correlated with short survival time of patients after radical surgery(p=0.023; p=0.107).Conclusion:1. Survivin and Psmd10 might be associated with the occurrence and progress of pancreatic ductal adenocarcinoma.2. Survivin and Psmd10 may have synergistic effect in the occurrence and progress of pancreatic ductal adenocarcinoma.3. Survivin and Psmd10 can indicate the prognosis of pancreatic ductal adenocarcinoma.更多还原