美國俄亥俄大學(xué)綜合癌癥中心的研究人員在檢查肺癌患者的血液時(shí)發(fā)現(xiàn)，其血漿中小分子RNA（miRNA）的特征圖形存在異常,，根據(jù)這種特殊的識(shí)別標(biāo)記,，可分析出當(dāng)前的疾病狀況和侵襲性。該發(fā)現(xiàn)可能在CT掃描發(fā)現(xiàn)腫瘤之前28個(gè)月,，就檢測(cè)出某人罹患肺癌的風(fēng)險(xiǎn),，使驗(yàn)血診斷肺癌成為可能。該發(fā)現(xiàn)公布在最新一期的美國《國家科學(xué)院院刊》（PNAS）上,。
miRNA是一組約21到23個(gè)堿基的不編碼的單鏈小分子RNA,，起著調(diào)節(jié)與機(jī)體生長、發(fā)育,、疾病發(fā)生過程有關(guān)的基因表達(dá)的作用,。miRNA有著很強(qiáng)的預(yù)兆性，在用一些靈敏手段如螺旋CT掃描之類的方法檢測(cè)到腫瘤之前,，即可先期在血漿里檢測(cè)到出現(xiàn)異常的miRNA,，從而提早診斷出癌癥。
研究小組在一次用螺旋CT掃描篩查肺癌臨床試驗(yàn)中,，發(fā)現(xiàn)了這種可作為識(shí)別標(biāo)記的特殊miRNA分子圖形,。1035名受試者年齡都在50歲以上，20年來每天至少抽一盒煙,。所有受試者在連續(xù)5年內(nèi)每年都要進(jìn)行CT掃描,，并提供血樣、痰樣和尿樣,。研究小組分析了28個(gè)腫瘤樣本和24個(gè)正常肺組織樣本,，檢查其miRNA分子圖形，發(fā)現(xiàn)腫瘤樣本中miRNA的生長率提高,，而在正常樣本中的生存率卻很低,。
研究小組利用識(shí)別標(biāo)記miRNA對(duì)從20名受試者采集的血樣分析后，發(fā)現(xiàn)了18名肺癌患者,，并在一年多以后經(jīng)螺旋CT掃描證實(shí),。為了進(jìn)一步確證,，他們還檢測(cè)了第二輪采集的血樣，這些樣本來自另一項(xiàng)類似但不相關(guān)的肺癌試驗(yàn),。他們從15名患者中識(shí)別出12名,，也在超過1年后被螺旋CT掃描確認(rèn)。研究人員估計(jì),，在螺旋CT掃描能檢出腫瘤之前28個(gè)月,，就能在血液中探測(cè)到識(shí)別標(biāo)記miRNA。
該研究負(fù)責(zé)人卡羅·克羅斯說：“我們的目標(biāo)是找出能預(yù)測(cè)腫瘤生長和發(fā)展的生物標(biāo)記,，提高肺癌診斷和治療效果,。這些發(fā)現(xiàn)提高了觀測(cè)能力，我們能在用螺旋CT作出臨床疾病檢測(cè)之前,，就檢測(cè)到在血漿中循環(huán)的miRNA,。這也讓根據(jù)miRNA外形特征來發(fā)現(xiàn)高風(fēng)險(xiǎn)病人成為可能。”（生物谷Bioon.com）
生物谷推薦原文出處：
Proceedings of the National Academy of Sciences DOI： 10.1073/pnas.1103154108
Down-regulation of homeobox genes MEIS1 and HOXA in MLL-rearranged acute leukemia impairs engraftment and reduces proliferation
Orlovsky, Kira; Kalinkovich, Alexander; Rozovskaia, Tanya; Shezen, Elias; Itkin, Tomer; Alder, Hansjuerg; Ozer, Hatice Gulcin; Carramusa, Letizia; Avigdor, Abraham; Volinia, Stefano; Buchberg, Arthur; Mazo, Alex; Kollet, Orit; Largman, Corey; Croce, Carlo M.; Nakamura, Tatsuya; Lapidot, Tsvee; Canaani, Eli
Rearrangements of the MLL (ALL1) gene are very common in acute infant and therapy-associated leukemias. The rearrangements underlie the generation of MLL fusion proteins acting as potent oncogenes. Several most consistently up-regulated targets of MLL fusions, MEIS1, HOXA7, HOXA9, and HOXA10 are functionally related and have been implicated in other types of leukemias. Each of the four genes was knocked down separatelyin the human precursor B-cell leukemic line RS4;11 expressing MLL-AF4. The mutant and control cells were compared for engraftmentin NOD/SCID mice. Engraftment of all mutants into the bone marrow (BM) was impaired. Although homing was similar, colonizationby the knockdown cells was slowed. Initially, both types of cells were confined to the trabecular area; this was followedby a rapid spread of the WT cells to the compact bone area, contrasted with a significantly slower process for the mutants.In vitro and in vivo BrdU incorporation experiments indicated reduced proliferation of the mutant cells. In addition, theCXCR4/SDF-1 axis was hampered, as evidenced by reduced migration toward an SDF-1 gradient and loss of SDF-1–augmented proliferationin culture. The very similar phenotype shared by all mutant lines implies that all four genes are involved and required forexpansion of MLL-AF4 associated leukemic cells in mice, and down-regulation of any of them is not compensated by the others.
