美国俄亥俄大学综合癌症中心的研究人员在检查肺癌患者的血液时发现，其血浆中小分子RNA（miRNA）的特征图形存在异常，根据这种特殊的识别标记，可分析出当前的疾病状况和侵袭性。该发现可能在CT扫描发现肿瘤之前28个月，就检测出某人罹患肺癌的风险，使验血诊断肺癌成为可能。该发现公布在最新一期的美国《国家科学院院刊》（PNAS）上。
miRNA是一组约21到23个碱基的不编码的单链小分子RNA，起着调节与机体生长、发育、疾病发生过程有关的基因表达的作用。miRNA有着很强的预兆性，在用一些灵敏手段如螺旋CT扫描之类的方法检测到肿瘤之前，即可先期在血浆里检测到出现异常的miRNA，从而提早诊断出癌症。
研究小组在一次用螺旋CT扫描筛查肺癌临床试验中，发现了这种可作为识别标记的特殊miRNA分子图形。1035名受试者年龄都在50岁以上，20年来每天至少抽一盒烟。所有受试者在连续5年内每年都要进行CT扫描，并提供血样、痰样和尿样。研究小组分析了28个肿瘤样本和24个正常肺组织样本，检查其miRNA分子图形，发现肿瘤样本中miRNA的生长率提高，而在正常样本中的生存率却很低。
研究小组利用识别标记miRNA对从20名受试者采集的血样分析后，发现了18名肺癌患者，并在一年多以后经螺旋CT扫描证实。为了进一步确证，他们还检测了第二轮采集的血样，这些样本来自另一项类似但不相关的肺癌试验。他们从15名患者中识别出12名，也在超过1年后被螺旋CT扫描确认。研究人员估计，在螺旋CT扫描能检出肿瘤之前28个月，就能在血液中探测到识别标记miRNA。
该研究负责人卡罗·克罗斯说：“我们的目标是找出能预测肿瘤生长和发展的生物标记，提高肺癌诊断和治疗效果。这些发现提高了观测能力，我们能在用螺旋CT作出临床疾病检测之前，就检测到在血浆中循环的miRNA。这也让根据miRNA外形特征来发现高风险病人成为可能。”（生物谷Bioon.com）
生物谷推荐原文出处：
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.
