生物谷報(bào)道：美國(guó)俄亥俄州Solove 研究所詹姆士腫瘤醫(yī)院腫瘤外科Bloomston M博士的研究表明：胰腺癌可能存在一個(gè)異于正常胰腺和慢性胰腺炎的微RNA表達(dá)模式,，微RNA表達(dá)模式可能用來判斷預(yù)后,，以上研究結(jié)果需在其他研究人群加以驗(yàn)證,。該研究結(jié)果發(fā)表在美國(guó)醫(yī)師協(xié)會(huì)雜志 2007年5月2日一期上,。
雖然整體微RNA表達(dá)模式在許多胚胎學(xué),、生理學(xué)和致癌過程都有研究報(bào)道,，但在胰腺導(dǎo)管癌微RNA的作用還不清楚,?；诖耍珺loomston M博士等人設(shè)計(jì)了本實(shí)驗(yàn),。標(biāo)本獲取于國(guó)立癌癥研究所命名的綜合癌癥中心收治的65例胰腺癌和42例慢性胰腺炎患者（2000年1月－2005年12月）,。所有患者均行根治性胰腺切除術(shù)；胰腺癌患者未行術(shù)前化療,。從切除胰腺腫瘤和臨近的胰腺正常組織及慢性胰腺炎標(biāo)本配對(duì),，RNA提取、雜合,、miRNA微列陣,。主要結(jié)果測(cè)量：從不同微RNA表達(dá)模式鑒定出某一表達(dá)模式可預(yù)測(cè)患者長(zhǎng)期生存率，并可從貌似正常胰腺,、慢性胰腺炎標(biāo)本鑒別胰腺癌,。微列陣分析的重要意義在于可從眾多微RNA中鑒別出可預(yù)測(cè)組織類型和預(yù)后的微RNA。多次測(cè)量校正后,，t檢驗(yàn)計(jì)算p值,。平均微RNA表達(dá)水平（高表達(dá)vs低表達(dá)）作為閾值形成卡普蘭-邁耶存活曲線與時(shí)序分析形成的階梯曲線加以比較。
結(jié)果顯示：經(jīng)交叉確認(rèn),，鑒定出21個(gè)高表達(dá)微RNA序列和4個(gè)低表達(dá)模式可從90%良性胰腺標(biāo)本準(zhǔn)確鑒別出胰腺癌,。15個(gè)高表達(dá)和8個(gè)低表達(dá)微RNA序列從慢性胰腺炎標(biāo)本鑒別出胰腺癌準(zhǔn)確率為93%。亞組6個(gè)微RNA序列可鑒別淋巴結(jié)陽(yáng)性胰腺癌長(zhǎng)期存活患者與2年內(nèi)死亡患者,。表達(dá)微RNA-196a-2 患者預(yù)后差,。[中位存活時(shí)間14.3月（95％可信區(qū)間12.4-16.2）vs 26.5月（95%可信區(qū)間23.4-29.6,；p=0.009],。
原文出處：
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
作者簡(jiǎn)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.
