鉴定CRC肝转移的分子亚型
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By LabMedica International staff writers Posted on 03 Jun 2018 |
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图片：MSI分析系统1.2版是一种荧光多重PCR方法，可检测微卫星不稳定性(MSI)，它是一种基因组的不稳定性（图片蒙Promega公司惠赐）。
转移是癌症相关死亡的首要原因，往往广泛散布，因此主流观点认为转移总是无所不在。
研究发现了一种大肠癌(CRC)，它在肝脏里形成局部的转移性肿瘤，此时仍然容易治疗。 研究反复证明，CRC有限肝转移的患者接受肝切除术后生存期很长，有机会研究寡转移的分子基础。
美国伊利诺伊州芝加哥大学(www.uchicago.edu)的科学家组成的一个综合小组联用RNA测序、靶向组合测序、微RNA分析和/或微卫星不稳定性测定，测定多达121名原发性CRC肝转移患者样本的特征。用美国加利福尼亚州圣克拉拉Affymetrix公司(www.affymetrix.com)基于阵列的miRNA 测得116份样本的特征谱，他们又用美国加利福尼亚州圣迭戈市Illumina公司(www.illumina.com)的HiSeq仪器对95例转移肿瘤进行转录组测序。
科研小组对59例病例的肿瘤样本和相应的正常样本进行OncoPlus组合测序，并使用美国威斯康辛州麦迪逊Promega公司(www.promega.com)的MSI 1.2临床测定评估89份转移肿瘤样本的微卫星不稳定性模式。癌症基因组图谱(Cancer Genome Atlas)这样的行动产生的CRC基因组数据伪部分肿瘤分类策略提供了信息。
研究人员发现转移到肝脏的CRC有三种分子亚型，包括一种总体生存期更长的寡转移病。一部分更有利的CRC肝转移病例表现出干扰素与其它免疫信号转导途径“独立于微卫星不稳定性”的活化，同时NRAS、CDK12和EBF1等基因发生突变。科研小组报道，虽然中度肿瘤亚型有VEGFA扩增以及NOTCH1突变、PIK3C2B突变和E2F/MYC途径的活化，这种分子特征称为“经典”。风险更高的“基质”CRC肝转移肿瘤含有VEGFA扩增以及基质、间质和新生血管的分子标记。
科研小组指出，轻度或中度肿瘤患者及临床风险分值低者10年平均生存率为94%。相较而言，45%的人当转移属于中度经典亚型且临床风险分值高或临床风险低但属于不利的基质肿瘤亚型时，生存期达到10年。10年生存率甚至更可怕，基质CRC肝转移且临床风险分值高的病例只有19%。该研究的论文发表于2018年5月4日的《自然》杂志《通信》分册。
芝加哥大学>>> www.uchicago.edu
Affymetrix >>> www.affymetrix.com
Illumina >>> www.illumina.com
Promega公司 >>> www.promega.com
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