CDKN2A
CDKN2B公司
PTEN公司
肿瘤科
比例危险模型
生存分析
生物
内科学
癌症
医学
基因
癌症研究
遗传学
信号转导
PI3K/AKT/mTOR通路
作者
L. Magnus Bäcklund,Bo Nilsson,Helena Goike,Esther Schmidt,Lu Liu,Koichi Ichimura,V. Peter Collins
出处
期刊:PubMed
日期:2003-09-15
卷期号:9 (11): 4151-8
被引量:19
摘要
Glioblastoma (GB, WHO grade IV) is the most common primary brain tumor in adults. Survival is typically <1 year but varies between a few months and a couple of years. The aim of the study was to find novel genetic prognostic factors in a well-defined GB series.The survival data on 129 GBs were correlated with the results of a detailed analysis of 9 genes. These included 3 genes coding for proteins in the p53 pathway (i.e., TP53, p14(ARF), and MDM2), 4 in the Rb1 pathway (i.e., CDKN2A, CDKN2B, RB1, and CDK4), as well as PTEN and epidermal growth factor receptor.We found that abnormalities in any of the four genes (CDKN2A, CDKN2B, RB1, and CDK4) coding for components of the Rb1 pathway were associated with shorter survival (P = 0.002). In combination with loss of wild-type PTEN, the association was even stronger (P < 0.001), the median survival being 166 days as compared with the group without these abnormalities where the median postoperative survival was 437 days. The survival difference remained statistically significant in Cox' regression analysis adjusting for age (P = 0.012).The findings indicate that knowledge of the molecular genetic abnormalities in GBs provides important data in assessing individual patients. As additional advances in our understanding of the molecular genetics and cell biology of gliomas are made, in addition to providing prognostic information, such data may also provide targets for innovative therapy in the individual case.
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