摘要
背景与目的:我国前列腺癌的发病率逐年上升,就诊时多为晚期患者,内分泌治疗后有效期短,继续治疗困难。胰岛素样生长因子Ⅱ(insulin-likegrowthfactorⅡ,IGF-Ⅱ)可促进多种细胞的增殖,抑制细胞凋亡;其表达受到基因印迹的调控,且基因印迹状态的改变与多种肿瘤的发生相关。本研究拟检测晚期前列腺癌组织中IGF-Ⅱ的印迹状态,并探讨印迹基因丢失与疾病进展的关系。方法:应用限制性酶切片段长度多态性分析法(restrictivefragmentlengthpolymorphism,RFLP),检测41例前列腺癌、27例前列腺增生和13例正常前列腺组织中的IGF-Ⅱ基因印迹状态。结果:前列腺癌、前列腺增生和正常前列腺组织中IGF-Ⅱ杂合子基因型分别为70.7%(29/41)、55.5%(15/27)和61.5%(8/13);58.6%(17/29)的前列腺癌组织中发生了IGF-Ⅱ的印迹丢失,高于前列腺增生组织(13.3%,P<0.05)和正常前列腺组织(12.5%,P<0.05)中的印迹丢失率。IGF-Ⅱ基因印迹状态与前列腺癌患者年龄无相关性,也与内分泌治疗前患者的血前列腺特异抗原值、伴发骨转移以及癌细胞的分化程度无显著相关。而全雄激素阻断治疗后,有印迹丢失的前列腺癌患者的1年无疾病进展生存率较无印迹丢失的患者低(70.0%vs.100.0%,P=0.039)。结论:晚期前列腺癌组织中IGF-Ⅱ基因印迹丢失发生率明显增高,并且印迹丢失与前列腺癌内分泌治疗后的进展恶化相关。
BACKGROUND ＆ OBJECTIVE. The incidence of prostate cancer is increasing rapidly in China, and most patients are advanced cases when they were confirmed. Advanced prostate cancer is very difficult to control, although the patients could get transient recovery after total androgen blockade. Insulin-like growth factor Ⅱ （IGF-Ⅱ ） can improve cell proliferation and inhibit cell apoptosis. Loss of imprinting （LOI） of IGF-Ⅱ , or activation of the normally silent and maternally inherited allele, was discovered in some types of cancer. Our study was to explore the genomic imprinting of IGF-Ⅱ in prostate cancer and its correlation to disease progression. METHODS. LOI of IGF- Ⅱ in 41 specimens of prostate cancer, 27 specimens of benign prostate hyperplasia, and 13 specimens of normal prostate tissue was detected by polymerase chain reaction-based restrictive fragment length polymorphism （PCR-RFLP） analysis. RESULTS. Rates of heterozygote of IGF- Ⅱ DNA were 70.7% （29/41） in prostate cancer group, 55.5% （15/27） in benign prostate hyperplasia group, and 61.5% （8/13） in normal prostate tissue group. In the specimens with IGF-Ⅱ DNA heterozygote, the occurrence rate of LOI of IGF- Ⅱ was significantly higher in prostate cancer than in benign prostate hyperplasia and normal prostate tissue （58.6% vs. 13.3% and 12.5%, P〈0.05）. LOI of IGF-Ⅱ had no correlation to patients＇ age, serum level of prostate-specific antigen （PSA）, presence of bone metastasis, and cell differentiation before endocrinotherapy. Received total androgen blockade, the 1-year progressfreely survival rate was significantly lower in the patients with LOI of IGF-Ⅱ than in the patients without LOI of IGF-Ⅱ （70% vs. 100%, P=0.039）. CONCLUSION. LOI of IGF-Ⅱ occurred frequently in advanced prostate cancer, and may be correlated to progression of prostate cancer after total androgen blockade.
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2006年第6期765-770,共6页
Chinese Journal of Cancer
基金
广东省自然科学基金项目(No.04105339)~~
关键词
基因印迹
前列腺肿瘤
胰岛素样生长因子
印迹状态
肿瘤进展
Genomic imprinting
Prostate neoplasm
Insulin-like growth factor
Imprinting status
Cancer progress
