Pin1与CyclinD1在肾透明细胞癌中的表达及意义

发布时间：2018-06-23 17:31

本文选题：肾透明细胞癌 + 肾细胞癌　；参考：《天津医科大学》2014年硕士论文

【摘要】：目的肾细胞癌(renal cell carcinoma, RCC)是泌尿生殖系统中最常见的恶性肿瘤之一,发病率占全身恶性肿瘤的3%,仅次于膀胧癌,居泌尿系肿瘤第二位。由于缺乏早期诊断标志,导致肾癌患者高比例的肿瘤转移,其中位生存期约为13个月,在肾细胞癌的诊断和治疗上有待于寻找新的作用靶点。在肾细胞癌中,肾透明细胞癌(clear cell renal cell carcinoma, CCRCC)类型约占65%-80%。肿瘤的发生是在基因和基因水平上多步骤、多因素的过程,最终导致不可控制的细胞增殖、转化和死亡。蛋白质序列中的丝氨酸/苏氨酸-脯氨酰键的磷酸化,是控制细胞周期循环、调节细胞增殖和分化的关键性信号调节机制。Pinl是肽基脯氨酰异构酶家族成员之一,它能使蛋白质中磷酸化的丝氨酸/苏氨酸-脯氨酰键异构化,由顺式变为反式,调节磷酸化蛋白质活性。Pinl的过表达可能参与了多种肿瘤的发生发展。CyclinD1是G1/S转换的限速控制因素,抑制CyclinD1的活性,可以使细胞受阻于G1期,限制瘤细胞的增殖,从而抑制肿瘤生长。研究发现,CyclinD1在多种肿瘤中过表达。本研究采用免疫组化法检测Pinl与CyclinD1蛋白在肾透明细胞癌及癌旁肾脏组织中的表达情况及它们之间的相关性,探讨其在肾透明细胞癌中的作用。材料与方法本研究所使用病例取自天津泌尿外科研究所、天津医科大学第二医院泌尿外科2007年6月～2009年1月手术切除肾透明细胞癌组织标本且临床资料齐备者102例。男64例,女38例；年龄30-81岁,平均56岁。按照WHO分级标准,G133例,G247例,G322例。采用ACJJ分期,Ⅰ期44例,Ⅱ期28例,Ⅲ期24例,Ⅳ期6例。另取肿瘤旁2cm区域的肾组织70例,作为对照组。所有染色切片均由两位富有经验的病理医生在同一条件下用光学显微镜采用双盲法阅片。用免疫组化SP法检测Pinl和CyclinD1的表达。结果判定：Pinl蛋白表达定位于细胞浆和(或)细胞核。根据其染色强度计分：无染色为0,淡红色为1,红色为2,橘红色为3；按染色阳性细胞百分率计分：阳性细胞百分率25%者为0,阳性细胞百分率25%-49%者为1,阳性细胞百分率50%-74%者为2,≥75%者为3。最后判断标准为上述两项得分相乘,得分≥3分为过度表达。CyclinD1蛋白表达定位于细胞核和(或)细胞浆,阳性细胞率小于10%为阴性(-),阳性细胞率大于等于10%为阳性(+)。对本研究中102例患者进行术后随访,随访其术后远处转移、局部复发、5年生存率等指标,随访时间为2011年6月～2014年2月。应用SPSS12.0医学统计软件,对Pinl和CyclinD1的表达与临床病理特征的关系用卡方检验,P0.05为有统计学意义。结果 1.Pinl和CyclinD1在肾透明细胞癌组织中的表达在癌旁组织中,Pinl蛋白的过表达率为11.43%；在肾透明细胞癌组织中,Pinl蛋白的过表达率为68.63%,在肾癌组织中Pinl的表达强度显著高于癌旁正常肾脏组织。肾癌组织中的过表达率比癌旁组织明显升高,两组间比较显示差异有统计学意义(P0.01)。 CyclinD1的表达主要位于细胞核,强阳性时胞浆尚有表达。本研究显示,CyclinD1在癌旁组织中仅有极少量阳性表达,大多数呈不表达。CyclinD1在肾透明细胞癌中的表达率为62.75%,明显高于癌旁组织的表达率8.57%。两组间比较有统计学差异(P0.01)。 2.Pinl和CyclinD1在肾透明细胞癌中的表达与临床病理特征的关系 Pinl的过表达与患者年龄、性别、肿瘤大小、病理分级等参数无显著相关,与临床分期呈正相关(P0.05)。CyclinD1的表达与临床分期也呈正相关(P0.05),而与患者的年龄、性别、病理分级等参数无显著相关。关于患者术后随访情况,102例肾透明细胞癌患者均获随访。所有患者均术后随访5年,其中有2例患者失访,2例因其他疾病和意外死亡而不计入随访样本量,对余下98例患者进行随访统计。根据统计结果,Pinl的过表达及cyclinD1的表达与患者远期复发率和5年存活率等参数并无显著相关(P0.05)。 3.肾透明细胞癌中Pinl和CyclinD1表达的相关性在Pinl过表达的70例肾透明细胞癌中,50例的CyclinD1呈现阳性表达,Pinl低表达的32例肾透明细胞癌中,有18例的CyclinD1蛋白呈阴性,二者在肾透明细胞癌中的表达呈显著正相关(P0.01)。结论 1.Pinl在肾透明细胞癌组织中的表达明显高于癌旁肾脏组织。CyclinD1在肾透明细胞癌组织中的表达明显高于癌旁肾脏组织。 2.Pinl的过表达与肾透明细胞患者的年龄、性别、肿瘤大小、病理分级等无显著相关,与临床分期呈正相关。CyclinD1的表达与年龄、性别、组织类型、病理分级等无显著相关,与临床分期呈正相关。 3.Pinl及CyclinD1与肾透明细胞癌患者的复发率、转移率、生存率等预后参数无明显相关。 4.Pinl与CyclinD1在肾透明细胞癌中的表达密切相关,提示Pinl的过表达可能促进CyclinD1的表达,Pinl可能为CyclinD1的上层调控因素。Pinl和CyclinD1异常表达可能共同参与肾透明细胞癌的发生、发展。
[Abstract]:objective
Renal cell carcinoma (RCC) is one of the most common malignant tumors in the genitourinary system. The incidence is 3% of the malignant tumor of the whole body. It is second only to bladder cancer and is the second place in the urinary tumor. Due to the lack of early diagnosis, it leads to a high proportion of tumor metastases in the patients with renal cancer, with a survival time of about 13 months in renal cell carcinoma. The diagnosis and treatment of renal cell carcinoma (clear cell renal cell carcinoma, CCRCC) are about 65%-80%. in renal cell carcinoma.
The occurrence of tumor is the process of multistep and multiple factors at the gene and gene level, which eventually leads to the non controlled cell proliferation, transformation and death. The phosphorylation of serine / threonine prolyl key in the protein sequence is the key signal regulating mechanism for controlling cell cycle cycle, regulating cell proliferation and differentiation.Pinl is the peptide based proline One of the members of the family of aminoacyl isomerase, which can make the phosphorylated serine / prolyl isomerization of phosphorylated protein in the protein from cis to trans, regulating the overexpression of phosphorylated protein activity.Pinl may participate in the development of a variety of tumors and.CyclinD1 is the limiting factor of G1/S conversion and inhibits the activity of CyclinD1. Cells are blocked in phase G1, which limits the proliferation of tumor cells and thus inhibits tumor growth. It is found that CyclinD1 is overexpressed in many tumors.
In this study, the expression of Pinl and CyclinD1 protein in renal clear cell carcinoma and adjacent renal tissue and the correlation between them were detected by immunohistochemical method, and the role of them in renal clear cell carcinoma was investigated.
Materials and methods
The cases were taken from the Tianjin Department of Urology, Tianjin Department of Urology, Second Hospital Affiliated to Tianjin Medical University in June 2007 ~ January 2009 to excision the renal clear cell carcinoma tissue specimens and the clinical data of 102 cases. Male 64 cases, female 38 cases, age 30-81 years, mean 56 years. According to WHO grading standard, G133 cases, G247 cases, G322 cases. AC JJ staging, 44 cases in stage I, 28 cases in stage II, 24 in stage III and 6 in stage IV. 70 cases of renal tissue in the 2cm region beside the tumor were taken as the control group. All the stained sections were used by two rich experienced pathologists on the same condition with the optical microscope to read the double blind method.
The expression of Pinl and CyclinD1 was detected by immunohistochemical SP. Results: the expression of Pinl protein was located in cytoplasm and (or) nuclei. According to its staining strength, no staining was 0, light red was 1, red was 2, orange red was 3, positive cells percentage was 0, positive cell percentage was 0, positive cell percentage was 25%- The percentage of positive cells was 1, the percentage of positive cell percentage 50%-74% was 2, the final judgment of 75% was 3., and the score was more than 3. The expression of over expression of.CyclinD1 protein was located in the nucleus and (or) cytoplasm, the positive cell rate was less than 10% as negative (-), the positive cell rate was more than 10% as positive (+).
In this study, 102 patients were followed up after operation, followed up with distant metastasis, local recurrence, 5 year survival rate and so on. The follow-up time was from June 2011 to February 2014. The relationship between the expression of Pinl and CyclinD1 and the clinicopathological features was checked with chi square, and P0.05 was statistically significant.
Result
Expression of 1.Pinl and CyclinD1 in renal clear cell carcinoma
In the para cancerous tissue, the overexpression of Pinl protein was 11.43%, and the overexpression rate of Pinl protein was 68.63% in the renal clear cell carcinoma tissue. The expression of Pinl in the renal carcinoma tissue was significantly higher than that in the normal renal tissue adjacent to the carcinoma. The overexpression rate in the renal carcinoma tissue was significantly higher than that in the para cancerous tissue. The difference between the two groups showed a significant difference. (P0.01).
The expression of CyclinD1 was mainly located in the nucleus and strongly positive cytoplasm was still expressed. This study showed that only a few positive expressions of CyclinD1 were found in the para cancerous tissues, and the expression rate of most of the non expression.CyclinD1 in the renal clear cell carcinoma was 62.75%, which was significantly higher than that of the para cancerous tissue 8.57%. two groups (P0.01).
Expression of 2.Pinl and CyclinD1 in clear cell renal cell carcinoma and their relationship with clinicopathological characteristics
There was no significant correlation between the overexpression of Pinl and the patient's age, sex, tumor size and pathological classification, and positive correlation with clinical stages (P0.05).CyclinD1 expression was also positively correlated with clinical stage (P0.05), but had no significant correlation with age, sex, pathological classification and other parameters.
102 cases of renal clear cell carcinoma were followed up for 5 years. All patients were followed up for 5 years, of which 2 cases were lost, 2 were followed up with other diseases and accidental deaths, and the remaining 98 patients were followed up. According to the statistical results, the expression of Pinl and the expression of cyclinD1 and patients There was no significant correlation between long-term recurrence rate and 5 year survival rate (P0.05).
Correlation between Pinl and CyclinD1 expression in 3. renal clear cell carcinoma
Of the 70 cases of Pinl overexpression of renal clear cell carcinoma, 50 cases of CyclinD1 showed positive expression. Of the 32 cases of renal clear cell carcinoma with low expression of Pinl, 18 cases of CyclinD1 protein were negative. The expression of the two in the renal clear cell carcinoma was significantly positive correlation (P0.01).
conclusion
The expression of 1.Pinl in the tissues of renal clear cell carcinoma was significantly higher than that in the paracancerous renal tissue. The expression of.CyclinD1 in the renal clear cell carcinoma tissue was significantly higher than that in the para cancerous renal tissue.
There was no significant correlation between the overexpression of 2.Pinl and the age, sex, tumor size and pathological grade of the patients with renal transparent cells. There was no significant correlation between the expression of.CyclinD1 and the age, sex, type of tissue, pathological grade and so on, which was positively correlated with the clinical stage.
3.Pinl and CyclinD1 were not correlated with the recurrence rate, metastasis rate, survival rate and other prognostic parameters of patients with clear cell renal cell carcinoma.
The expression of 4.Pinl and CyclinD1 is closely related to the expression of renal clear cell carcinoma, suggesting that the overexpression of Pinl may promote the expression of CyclinD1. Pinl may be the upper regulatory factor of CyclinD1, the abnormal expression of.Pinl and CyclinD1 may participate in the occurrence and development of renal clear cell carcinoma.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.11

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