来源
2007-5-30 20:19:24

JAMA:MicroRNA表达谱模式有助于诊断胰腺癌和胰腺炎

生物谷报道:美国俄亥俄州Solove 研究所詹姆士肿瘤医院肿瘤外科Bloomston M博士的研究表明:胰腺癌可能存在一个异于正常胰腺和慢性胰腺炎的微RNA表达模式,微RNA表达模式可能用来判断预后,以上研究结果需在其他研究人群加以验证。该研究结果发表在美医师协会杂志 2007年5月2一期上。

虽然整体微RNA表达模式在许多胚胎学、生理学和致癌过程都有研究报道,但在胰腺导管癌微RNA的作用还不清楚。基于此,Bloomston M博士等人设计了本实验。标本获取于国立癌症研究所命名的综合癌症中心收治的65例胰腺癌和42例慢性胰腺炎患者(20001月-200512月)。所有患者均行根治性胰腺切除术;胰腺癌患者未行术前化疗。从切除胰腺肿瘤和临近的胰腺正常组织及慢性胰腺炎标本配对,RNA提取、杂合、miRNA微列阵。主要结果测量:从不同微RNA表达模式鉴定出某一表达模式可预测患者长期生存率,并可从貌似正常胰腺、慢性胰腺炎标本鉴别胰腺癌。微列阵分析的重要意义在于可从众多微RNA中鉴别出可预测组织类型和预后的微RNA。多次测量校正后,t检验计算p值。平均微RNA表达水平(高表达vs低表达)作为阈值形成卡普兰-迈耶存活曲线与时序分析形成的阶梯曲线加以比较。
   
结果显示:经交叉确认,鉴定出21个高表达微RNA序列和4个低表达模式可从90%良性胰腺标本准确鉴别出胰腺癌。15个高表达和8个低表达微RNA序列从慢性胰腺炎标本鉴别出胰腺癌准确率为93%。亚组6个微RNA序列可鉴别淋巴结阳性胰腺癌长期存活患者与2年内死亡患者。表达微RNA-196a-2 患者预后差。[中位存活时间14.3月(95%可信区间12.4-16.2vs 26.5月(95%可信区间23.4-29.6p=0.009]

 

 

原文出处:

JAMA    Vol. 297 No. 17, pp. 1853-1946, May 2, 2007

MicroRNA Expression Patterns to Differentiate Pancreatic Adenocarcinoma From Normal Pancreas and Chronic Pancreatitis
Mark Bloomston; Wendy L. Frankel; Fabio Petrocca; Stefano Volinia; Hansjuerg Alder; John P. Hagan; Chang-Gong Liu; Darshna Bhatt; Cristian Taccioli; Carlo M. Croce
JAMA. 2007;297:1901-1908.
ABSTRACT | FULL TEXT | PDF

 

 

作者简介:

Carlo M. Croce, M.D.

Ohio State University Cancer Center
Columbus, Ohio
1-800-293-5066

Dr. Croce has been investigating the genes and the genetic mechanisms involved in the pathogenesis of human cancer, focusing on the early genetic changes. He discovered the juxtaposition of the human immunoglobulin genes and the MYC oncogene, the deregulation of MYC in Burkitt lymphoma, and cloned and characterized the BCL2 gene involved in follicular lymphoma.

Croce's group focuses on the initiating events responsible for the pathogenesis of human hematopoietic malignancies and on the early events involved in the pathogenesis of human cancer; head and neck cancer and gastrointestinal cancer. These studies have led to the identification of several genes that play an important role in the initiation of several important human neoplastic diseases:

ALL1, that is involved in human acute leukemias, including acute lymphoblastic leukemia, acute myelogenous leukemia, acute myelomonocytic leukemia and acute monocytic leukemia. Dr. Croce's group has also shown that ALL1 can fuse with itself (this mechanism is called ‘self fusion') leading to acute myelogenous leukemia. They have also identified several gene targets of ALL1, including a gene named ARP, the expression of which is lost in acute leukemias carrying chromosome translocations involving the ALL1 locus at 11q23.

TCL1, that is involved in chronic T cell leukemia and adult T cell leukemia.

FHIT, that is involved early on in the pathogenesis of lung cancer, nasopharyngeal and esophageal cancer, gastrointestinal cancer, breast cancer, head and neck cancer, and cervical cancer. This gene contains the most common fragile site of the human genome, FRA3B, that appears to be the target for genetic rearrangements caused by a variety of environmental carcinogens.

Dr. Croce and his research group have also continued studies on the role of TAL1/ SCL/TCL5 in the pathogenesis of human leukemias and in hematopoietic differentiation. They have developed a TAL1 transgenic mouse model, in which overexpression of the gene leads to acute leukemia or high grade lymphoma.

 

相关报道:

microRNA的肿瘤抑制因子角色

体外肿瘤抑制分子MicroRNA 

Cell:与心脏发育有关的重要遗传因素microRNA


PNAS:MicroRNA水平的干细胞开关被确定

胰脏癌中异常表现的microRNA有助于新诊断方法的研发

在胰腺癌中超常表达的microRNA 

Science:科学家发现microRNA的定位机制

一对控制白血病原癌基因的microRNA分子 

 

一类小分子RNA可鉴别胰腺癌

美科学家首次识别出与胰腺癌有关的癌干细胞 

 

印科学家发现新的胰腺炎基因cathepsin B 

 

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