Liu Zhuo-Wei, Zhou Fang-Jian, Luo Yan-Min, Qin Zi-Ke, Wang Du-Jian, Luo Jun-Hang, Han Hui, Li Yong-Hong, Wang Huan
State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, 510060, P. R. China.
Ai Zheng. 2006 Jun;25(6):765-70.
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.
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.
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 progress-freely 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).
LOI of IGF-II occurred frequently in advanced prostate cancer, and maybe correlated to progression of prostate cancer after total androgen blockade.
中国前列腺癌的发病率正迅速上升,且多数患者确诊时已为晚期病例。晚期前列腺癌很难控制,尽管患者在接受全雄激素阻断治疗后可能会获得短暂缓解。胰岛素样生长因子II(IGF-II)可促进细胞增殖并抑制细胞凋亡。在某些类型的癌症中发现了IGF-II的印记丢失(LOI),即通常沉默的母系遗传等位基因被激活。本研究旨在探讨前列腺癌中IGF-II的基因组印记及其与疾病进展的相关性。
采用基于聚合酶链反应的限制性片段长度多态性(PCR-RFLP)分析,检测41例前列腺癌标本、27例良性前列腺增生标本和13例正常前列腺组织标本中IGF-II的LOI情况。
前列腺癌组、良性前列腺增生组和正常前列腺组织组中IGF-II DNA杂合子率分别为70.7%(29/41)、55.5%(15/27)和61.5%(8/13)。在IGF-II DNA杂合子标本中,前列腺癌中IGF-II的LOI发生率显著高于良性前列腺增生和正常前列腺组织(58.6%对13.3%和12.5%,P<0.05)。IGF-II的LOI与患者年龄、血清前列腺特异性抗原(PSA)水平、骨转移情况及内分泌治疗前的细胞分化无关。接受全雄激素阻断治疗后,IGF-II发生LOI的患者1年无进展生存率显著低于未发生LOI的患者(70%对100%,P=0.039)。
IGF-II的LOI在晚期前列腺癌中频繁发生,可能与全雄激素阻断治疗后前列腺癌的进展相关。