ERK及其磷酸化在晚期前列腺癌组织中的表达及意义

发布时间：2018-08-20 12:26

【摘要】：目的:前列腺癌在55岁以上的男性人群中的发病率较高,且随着年龄的增长而升高。近年来,前列腺癌的发病率已跃居男性恶性肿瘤第二位,在我国,其发病率也逐年增高,占男性恶性肿瘤第三位,病死率仅次于肺癌。丝裂原活化蛋白激酶(MAPK)是细胞内信号传递途径的共同通道及汇聚点,细胞外信号调节激酶(ERK)是其家族成员之一。大量研究表明在恶性肿瘤中均存在ERK信号转导通路,该通路在恶性肿瘤中有至关重要的作用,在前列腺癌中也存在着该通路,但目前,国内外对ERK信号转导通路在前列腺癌中的研究倾向于肿瘤的分期、分级,对前列腺癌患者的生存预后研究较为缺乏,本次研究不仅对前列腺癌的侵袭力、PSA水平做了研究,而且对前列腺癌患者的生存预后做了相关性分析,为ERK信号转导通路影响前列腺癌患者的预后提供了相关的临床数据。本次研究主要探讨细胞外信号调节激酶(ERK)及其磷酸化状态(p-ERK)在前列腺增生组织和晚期前列腺癌组织中的表达,以及能否作为判断晚期前列腺癌预后的标志物。方法:选取大连医科大学附属第一医院2008年10月到2011年2月具有完整病例资料的晚期前列腺癌组织40例及前列腺增生组织20例,其中晚期前列腺癌组织40例,均为T3/T4/Nx-1Mx期,因尿路梗阻均行经尿道前列腺电切术+双侧睾丸切除术,所有患者术后均行规律内分泌治疗,且排除其他肿瘤病史;前列腺增生组织20例,均因尿路梗阻行经尿道前列腺电切术。患者年龄在58-86岁之间,平均年龄73岁,手术切除组织标本均经10%甲醛固定24小时后,做常规石蜡包埋处理。应用免疫组织化学(Envision)法检测前列腺增生组织(benign prostatic hyperplasia,BPH)及晚期前列腺癌(PCa)组织中ERK1/2及其磷酸化状态(p-ERK1/2)的表达,并分析其与晚期前列腺癌转移(侵袭力)、Gleason评分、PSA水平以及生存时间的关系。结果:(1)ERK1/2的表达:在前列腺增生组织中阳性表达率为55.0%,在晚期前列腺癌组织中阳性表达率为82.5%,具有显著性差异(P0.05);在晚期前列腺癌转移组与未转移组中阳性表达率分别为84.2%、80.9%,无显著性差异(P0.05);在Gleason评分7分与Gleason评分≤7分中的阳性表达率分别为91.3%、70.6%,无显著性差异(P0.05);在PSA20ng/ml与PSA≤20ng/ml中的阳性表达率分别为87.5%、62.5%,无显著性差异(P0.05);在生存时间5年与生存时间≤ 5年中的阳性表达率分别为84.2%、80.9%,无显著性差异(P0.05);(2)p-ERK1/2的表达:前列腺增生组织中阳性表达率为35.0%,晚期前列腺癌组织中阳性表达率为75.0%,有显著性差异(P0.05);在Gleason评分7分与Gleason评分≤7分中的阳性表达率分别为73.9%、76.5%,无显著性差异(P0.05);在PSA20ng/ml与PSA≤20ng/ml中的阳性表达率分别为78.1%、62.5%,无显著性差异(P0.05);在晚期前列腺癌转移组和未转移组中阳性表达率分别为:61.9%、89.5%,有显著性差异(P0.05);在生存时间5年与生存时间≤5年组中阳性表达率分别为:57.9%、90.5%,有显著性差异(P0.05)。结论:ERK1/2、p-ERK1/2在晚期前列腺癌组织中高表达,ERK1/2磷酸化与晚期前列腺癌侵袭力(转移)及预后有关。
[Abstract]:Objective: The incidence of prostate cancer in men over 55 years old is higher, and it increases with age. In recent years, the incidence of prostate cancer has jumped to the second place in male malignant tumors. In China, the incidence of prostate cancer has also increased year by year, accounting for the third place in male malignant tumors, mortality is only second to lung cancer. Mitogen-activated protein kinase (MA) Extracellular signal-regulated kinase (ERK) is one of the family members of PK, which is the common pathway and convergence point of intracellular signal transduction pathway. A large number of studies have shown that ERK signal transduction pathway exists in malignant tumors. This pathway plays an important role in malignant tumors and also exists in prostate cancer. However, at present, it is widely used in prostate cancer at home and abroad. The research of ERK signal transduction pathway in prostate cancer tends to staging and grading of tumor, and the study of survival and prognosis of prostate cancer patients is scarce. This study not only studied the invasiveness and PSA level of prostate cancer, but also analyzed the correlation between the survival and prognosis of prostate cancer patients, and affected the ERK signal transduction pathway. This study was designed to investigate the expression of extracellular signal-regulated kinase (ERK) and its phosphorylated state (p-ERK) in prostate hyperplasia and advanced prostate cancer, and whether they can be used as prognostic markers of advanced prostate cancer. From October 2008 to February 2011, the First Affiliated Hospital had complete data of 40 cases of advanced prostate cancer and 20 cases of benign prostatic hyperplasia. Among them, 40 cases of advanced prostate cancer were of stage T3/T4/Nx-1Mx. All patients underwent transurethral resection of prostate and bilateral orchiectomy due to urinary obstruction. 20 cases of benign prostatic hyperplasia were treated by transurethral resection of prostate due to urinary tract obstruction. The patients were aged from 58 to 86 years, with an average age of 73 years. The expression of ERK1/2 and its phosphorylated state (p-ERK1/2) in benign prostatic hyperplasia (BPH) and advanced prostate cancer (PCa) tissues was analyzed. The relationship between the expression of ERK1/2 and metastasis (invasiveness), Gleason score, PSA level and survival time of advanced prostate cancer was analyzed. The positive expression rate was 82.5% in advanced prostate cancer (P 0.05), 84.2% in metastatic group and 80.9% in non-metastatic group (P 0.05), 91.3% in Gleason score 7 and 70.6% in Gleason score < 7, respectively. The positive expression rates of PSA20ng/ml and PSA < 20ng/ml were 87.5% and 62.5%, respectively, with no significant difference (P 0.05); the positive expression rates of PSA20ng/ml and PSA < 20ng/ml were 84.2% and 80.9% respectively, with no significant difference (P 0.05); (2) the expression of p-ERK1/2 in prostate hyperplasia tissues was 35.0% and in advanced prostatic hyperplasia tissues. The positive expression rate in adenocarcinoma tissues was 75.0% (P 0.05), 73.9% in Gleason score 7 and 76.5% in Gleason score < 7, respectively, with no significant difference (P 0.05), 78.1% in PSA20ng/ml and 62.5% in PSA < 20ng/ml, respectively, without significant difference (P 0.05). The positive expression rates of ERK1/2 and p-ERK1/2 were 61.9% and 89.5% respectively in the metastatic group and the non-metastatic group, with significant difference (P 0.05), and 57.9% and 90.5% respectively in the 5-year survival group and the 5-year survival group (P 0.05). Impact (metastasis) is associated with prognosis.
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.25
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本文编号：2193603